ABGC Certification Examination for Genetic Counselors — Questions and Answers

Question 1: What term describes the phenomenon where the expression of a gene depends on whether it was inherited from the mother or the father?

Genomic imprinting (Correct answer)
Incomplete penetrance
Anticipation
Variable expressivity

Correct answer: Genomic imprinting

Genomic imprinting is an epigenetic process by which gene expression is determined by the parental origin of the allele.

Question 2: In the United States, which law prohibits health insurers and employers from discriminating based on genetic information but does NOT cover life, disability, or long-term care insurance?

HIPAA
ADA
GINA (Correct answer)
ACA

Correct answer: GINA

The Genetic Information Nondiscrimination Act covers health insurance and employment only, leaving life, disability, and long-term care insurance uncovered.

Question 3: Variable expressivity in genetics means:

Some pathogenic variants are more severe than others in the same individual
The gene is only expressed in males
A gene is expressed in some tissues but not others
Individuals with the same pathogenic variant may show different degrees or types of clinical features (Correct answer)

Correct answer: Individuals with the same pathogenic variant may show different degrees or types of clinical features

Variable expressivity describes the range in clinical severity or phenotypic features seen among individuals who share the same pathogenic variant.

Question 4: According to ACMG/AMP variant classification guidelines, variants are classified into how many categories?

Five: pathogenic, likely pathogenic, uncertain significance, likely benign, benign (Correct answer)
Four: pathogenic, likely pathogenic, benign, likely benign
Two: pathogenic and benign only
Three: pathogenic, benign, unknown

Correct answer: Five: pathogenic, likely pathogenic, uncertain significance, likely benign, benign

The 2015 ACMG/AMP guidelines established a five-tier classification system: pathogenic, likely pathogenic, VUS, likely benign, and benign.

Question 5: Confined placental mosaicism (CPM) is a limitation unique to which prenatal diagnostic procedure?

Amniocentesis
Chorionic villus sampling (CVS) (Correct answer)
Fetal blood sampling
Cell-free DNA screening

Correct answer: Chorionic villus sampling (CVS)

CPM occurs in CVS because placental cells (trophoblast) may carry chromosomal abnormalities not present in the fetus, leading to false-positive results.

Question 6: The ACMG guideline criterion BS1 (allele frequency is greater than expected for disorder) is used as:

Evidence of uncertain significance
Moderate evidence of pathogenicity
Strong evidence of pathogenicity
Strong evidence of benign classification (Correct answer)

Correct answer: Strong evidence of benign classification

BS1 provides strong benign evidence when a variant's population frequency exceeds what would be expected if it caused a disease at the reported prevalence.

Question 7: Locus heterogeneity refers to the situation where:

A condition shows both dominant and recessive inheritance
Mutations at different gene loci can all cause the same clinical phenotype (Correct answer)
Multiple alleles at the same locus cause the same disease
One gene causes multiple different phenotypes

Correct answer: Mutations at different gene loci can all cause the same clinical phenotype

Locus heterogeneity means clinically similar conditions can result from variants in different genes, complicating genetic testing interpretation.

Question 8: Carrier screening for spinal muscular atrophy (SMA) is recommended for:

Only Ashkenazi Jewish individuals
Women over 35 years of age
Individuals with a family history of SMA only
All individuals of reproductive age regardless of ethnicity (Correct answer)

Correct answer: All individuals of reproductive age regardless of ethnicity

Current ACOG guidelines recommend expanded carrier screening, including SMA, for all individuals of reproductive age due to pan-ethnic prevalence.

Question 9: What is the term for a person who carries a gene for a genetic disorder but shows no symptoms?

Carrier (Correct answer)
Affected individual
Proband
Homozygote

Correct answer: Carrier

A carrier has one copy of a mutated gene but does not exhibit the disorder themselves.

Question 10: Which of the following is a key difference between genetic counseling and genetic testing?

Genetic counseling requires laboratory credentials
Genetic testing always includes counseling as part of the process
Genetic counseling is performed only by physicians
Genetic counseling addresses the psychological and informational needs surrounding genetic information, while testing provides molecular data (Correct answer)

Correct answer: Genetic counseling addresses the psychological and informational needs surrounding genetic information, while testing provides molecular data

Genetic counseling is a distinct psycho-educational process separate from the technical act of genetic testing.

Question 11: Which of the following best describes the 'duty to warn' dilemma in genetic counseling?

Requirement to disclose laboratory error rates
Obligation to warn clients about test costs
Balancing client confidentiality against potential serious harm to at-risk relatives (Correct answer)
Obligation to report all results to the state health department

Correct answer: Balancing client confidentiality against potential serious harm to at-risk relatives

The duty to warn weighs confidentiality against preventing serious, foreseeable, preventable harm to identifiable relatives.

Question 12: Why is psychological support essential in genetic counseling?

To conduct lab tests
To assist with pharmacy orders
To ensure emotional well-being and informed decisions (Correct answer)
To prepare billing documents

Correct answer: To ensure emotional well-being and informed decisions

Support helps clients cope with emotional stress related to risk, diagnosis, or decision-making.

Question 13: A genetic counselor uses the phrase 'positive result' when reporting an elevated carrier frequency finding. This language is problematic because:

Carrier status should never be disclosed verbally
It is too technical for most patients
Patients may interpret 'positive' as good news, causing misunderstanding (Correct answer)
It doesn't specify the gene involved

Correct answer: Patients may interpret 'positive' as good news, causing misunderstanding

The term 'positive result' is ambiguous and can be falsely reassuring; genetic counselors should use precise language like 'pathogenic variant identified'.

Question 14: A genetic counselor suspects a patient has not truly understood the recurrence risk discussed. The BEST next step is to:

Document that information was provided
Provide a pamphlet and schedule a follow-up
Use teach-back to reassess and re-explain with different framing (Correct answer)
Ask the referring physician to reinforce the information

Correct answer: Use teach-back to reassess and re-explain with different framing

Reassessing comprehension through teach-back and offering alternative explanations ensures genuine informed understanding.

Question 15: What does autosomal recessive inheritance mean?

Only one copy of a gene causes disease
Only females are affected
Two copies of a gene must be mutated (Correct answer)
Gene is located on a sex chromosome

Correct answer: Two copies of a gene must be mutated

Autosomal recessive inheritance means that an individual must inherit two copies of a mutated gene—one from each parent—to develop the associated disease. Individuals with only one mutated copy are typically carriers and do not show symptoms. The gene responsible is located on an autosome (a non-sex chromosome).

Question 16: A patient of advanced maternal age asks about the risk of chromosomal abnormalities. The counselor explains that the baseline risk for trisomy 21 at age 35 is approximately:

1 in 2,000
1 in 1,000
1 in 385 (Correct answer)
1 in 50

Correct answer: 1 in 385

At age 35, the risk for trisomy 21 is approximately 1 in 385, which has historically defined the threshold for discussing invasive prenatal diagnosis.

Question 17: Which ethical principle emphasizes doing good for the patient?

Beneficence (Correct answer)
Justice
Autonomy
Nonmaleficence

Correct answer: Beneficence

Beneficence is the ethical obligation to act in the best interest of the patient.

Question 18: A Caucasian individual (prior carrier risk about 1/25) tests negative on a CF panel with a 90% detection rate. What is the approximate residual carrier risk?

1/25
1/2,500
1/241 (Correct answer)
1/100

Correct answer: 1/241

(1/25 x 0.10) / [(1/25 x 0.10) + (24/25 x 1)] is about 1/241.

Question 19: When a genetic test result is reported as 'negative,' a genetic counselor should clarify that this means:

The patient is definitively unaffected and at population risk
The patient cannot be a carrier for the tested condition
No pathogenic variant was identified in the genes tested, but residual risk may remain (Correct answer)
No further testing is warranted under any circumstances

Correct answer: No pathogenic variant was identified in the genes tested, but residual risk may remain

A negative result means no variant was identified in the tested genes, but residual risk exists due to test sensitivity limits and the possibility of variants in untested genes.

Question 20: In a population where the frequency of a recessive allele (q) is 0.1, the expected carrier frequency under Hardy-Weinberg equilibrium is:

0.81 (81%)
0.18 (18%) (Correct answer)
0.02 (2%)
0.01 (1%)

Correct answer: 0.18 (18%)

Carrier frequency = 2pq = 2 × 0.9 × 0.1 = 0.18, meaning 18% of the population are heterozygous carriers.

Question 21: A woman's brother has cystic fibrosis (autosomal recessive), and she is unaffected. Before any testing, what is her risk of being a carrier?

2/3 (Correct answer)
1/4
3/4
1/2

Correct answer: 2/3

Of the unaffected offspring of two carriers, two of three expected genotypes are carriers, giving a 2/3 risk.

Question 22: What does autosomal dominant inheritance imply?

Condition is caused only when both gene copies are mutated.
One copy of a mutated gene can cause the condition. (Correct answer)
Condition only affects females.
Genes are only inherited from the mother.

Correct answer: One copy of a mutated gene can cause the condition.

A single copy of the mutated gene from either parent can cause the disorder.

Question 23: In clinical sequencing, 'analytical validity' refers to:

Whether knowing the result improves patient outcomes
The clinical significance of a detected variant
The ability of the test to accurately detect the specific variant it is designed to identify (Correct answer)
Whether a test measures what it claims to measure biologically

Correct answer: The ability of the test to accurately detect the specific variant it is designed to identify

Analytical validity measures the technical accuracy of a test in detecting or measuring what it is designed to detect, such as sensitivity and specificity for variant detection.

Question 24: Which role does a genetic counselor play in test interpretation?

Collect payment
Interpret results for patients (Correct answer)
Recommend medications
Diagnose patients

Correct answer: Interpret results for patients

Genetic counselors are healthcare professionals with specialized education and training in medical genetics and counseling. Their primary role is to interpret complex genetic test results for patients, explaining what the results mean for their health and their family. They also provide risk assessment, education, and support, helping patients make informed decisions about genetic testing and its implications.

Question 25: A laboratory reclassifies a previously reported VUS as likely pathogenic. What is the most appropriate next step?

Delete the original report from the record
Issue an amended report to the ordering provider so the patient can be recontacted (Correct answer)
Wait until the patient asks about updated results
Reclassify only if a relative also tests positive

Correct answer: Issue an amended report to the ordering provider so the patient can be recontacted

Reclassifications that affect care should be communicated through an amended report so the provider can recontact the patient.

Question 26: Next-generation sequencing (NGS) gene panels in clinical genetics typically involve:

Single-gene Sanger sequencing
Sequencing the entire genome at high depth
Targeted sequencing of selected disease-relevant genes (Correct answer)
Cytogenetic karyotyping

Correct answer: Targeted sequencing of selected disease-relevant genes

Clinical gene panels use NGS to simultaneously sequence a curated set of genes known to cause a specific disease or disease category.

Question 27: Which result indicates a disease-causing mutation?

Pathogenic (Correct answer)
Benign
VUS
Likely benign

Correct answer: Pathogenic

In genetics, a 'pathogenic' variant or mutation is one that is known to cause disease. This classification indicates a clear link between the genetic change and a specific health condition. Other options like benign or likely benign suggest no disease causation, while VUS (Variant of Uncertain Significance) means its impact is not yet known.

Question 28: Familial adenomatous polyposis (FAP) is caused by pathogenic variants in the APC gene and is characterized by:

Exclusively upper GI polyps with low malignant potential
Hamartomatous polyps throughout the GI tract
A few colonic polyps (fewer than 10) in adulthood
Hundreds to thousands of colonic adenomatous polyps with near-100% colorectal cancer risk if untreated (Correct answer)

Correct answer: Hundreds to thousands of colonic adenomatous polyps with near-100% colorectal cancer risk if untreated

Classic FAP involves hundreds to thousands of colorectal adenomas and carries essentially 100% lifetime risk of colorectal cancer without prophylactic colectomy.

Question 29: Repeat expansion testing using triplet-primed PCR or Southern blot is MOST commonly used to diagnose:

Gene fusions in cancer
Trinucleotide repeat expansion disorders such as Huntington disease or Fragile X syndrome (Correct answer)
Chromosomal aneuploidies
Mitochondrial DNA depletion syndromes

Correct answer: Trinucleotide repeat expansion disorders such as Huntington disease or Fragile X syndrome

Triplet-primed PCR and Southern blot are specialized techniques used to detect and size trinucleotide repeat expansions that cause conditions like Huntington disease and Fragile X.

Question 30: Which type of test examines many genes at once?

Physical exam
Biopsy
Single-gene testing
Panel testing (Correct answer)

Correct answer: Panel testing

Panel testing evaluates multiple genes associated with a condition or symptoms.

Question 31: The founder effect in genetics refers to:

Reduced genetic diversity in a population descended from a small founding group (Correct answer)
The founding of a genetic counseling clinic
The discovery of a new genetic variant by a researcher
The increased genetic diversity seen in hybrid populations

Correct answer: Reduced genetic diversity in a population descended from a small founding group

The founder effect occurs when a small isolated group establishes a new population, leading to high frequencies of alleles present in the original founders.

Question 32: What is the function of a gene?

Produce glucose
Regulate blood pressure
Carry genetic instructions (Correct answer)
Store calcium

Correct answer: Carry genetic instructions

A gene is a fundamental unit of heredity that carries genetic instructions from parents to offspring. These instructions are encoded in DNA and dictate the synthesis of proteins or functional RNA molecules, which in turn control the development, function, and maintenance of an organism. Genes are essentially the blueprints for all cellular processes and traits.

Question 33: During a session, a patient becomes visibly distressed upon learning about a hereditary cancer risk. The counselor's immediate priority should be:

Remind the patient that early detection improves outcomes
Continue reviewing test options to stay on schedule
Acknowledge the patient's emotional response and provide space to process (Correct answer)
Refer the patient immediately to a mental health professional

Correct answer: Acknowledge the patient's emotional response and provide space to process

Acknowledging distress and creating emotional space is foundational to patient-centered counseling before advancing to clinical information.

Question 34: When counseling a patient from a different cultural background regarding a hereditary condition, the genetic counselor should FIRST:

Request a formal cultural competency consult
Assume cultural beliefs will not affect decision-making
Proceed with standard counseling and adjust only if resistance is encountered
Ask the patient about their cultural values and beliefs related to genetics (Correct answer)

Correct answer: Ask the patient about their cultural values and beliefs related to genetics

Eliciting cultural context upfront ensures counseling is respectful, relevant, and effective for each individual patient.

Question 35: A genetic counselor is helping a patient communicate a hereditary risk to family members. The MOST appropriate counselor role is to:

Advise the patient not to disclose to avoid family anxiety
Require family members to attend the next counseling session
Provide the patient with tools and guidance to share the information themselves (Correct answer)
Contact family members directly on the patient's behalf

Correct answer: Provide the patient with tools and guidance to share the information themselves

The genetic counselor respects patient confidentiality by empowering the patient to share information rather than contacting relatives directly.

Question 36: Genetic counselors use Bayesian analysis in clinical genetics primarily to:

Estimate the population frequency of a variant
Calculate the cost-effectiveness of genetic tests
Combine prior probability with conditional information to derive a revised posterior probability of a genotype or diagnosis (Correct answer)
Determine the statistical power of a research study

Correct answer: Combine prior probability with conditional information to derive a revised posterior probability of a genotype or diagnosis

Bayesian analysis updates prior probability estimates using additional conditional information (e.g., normal test results, clinical features) to compute a posterior probability.

Question 37: Which risk model estimates breast cancer risk using personal factors such as age, reproductive history and biopsies, but incorporates only limited family history?

CanRisk/BOADICEA
BRCAPRO
Claus model
Gail model (Correct answer)

Correct answer: Gail model

The Gail model relies on personal risk factors with minimal family history and is not suited to hereditary cancer families.

Question 38: What does a variant of uncertain significance (VUS) indicate?

It is a lab error
It is always pathogenic
It is always benign
Its significance is not currently known (Correct answer)

Correct answer: Its significance is not currently known

A VUS means the genetic change has unknown impact on health or disease risk.

Question 39: What is genetic discrimination?

Health promotion strategy
Discrimination based on genetic information (Correct answer)
Offering additional medical care
Genetic counseling best practice

Correct answer: Discrimination based on genetic information

It refers to differential treatment based on a person’s genetic makeup, especially in employment or insurance.

Question 40: The term 'diagnostic yield' in clinical genetics refers to:

The number of variants reported per patient
The proportion of tested individuals who receive a molecular diagnosis from a given test (Correct answer)
The cost efficiency of a genetic test
The sensitivity of the test for detecting known pathogenic variants

Correct answer: The proportion of tested individuals who receive a molecular diagnosis from a given test

Diagnostic yield is the percentage of patients who receive a definitive molecular diagnosis, which varies by test type, clinical indication, and phenotype.

Question 41: A pregnant patient is found to have a fetal ultrasound showing an isolated echogenic bowel. This finding is associated with increased risk for which genetic condition?

Turner syndrome
Fragile X syndrome
Cystic fibrosis (Correct answer)
Trisomy 13

Correct answer: Cystic fibrosis

Echogenic bowel is a soft marker associated with cystic fibrosis, as swallowed meconium in an affected fetus can appear echogenic on ultrasound.

Question 42: Why is nondirectiveness important in genetic counseling?

It simplifies paperwork.
It promotes patient autonomy. (Correct answer)
It avoids legal responsibility.
It ensures quicker sessions.

Correct answer: It promotes patient autonomy.

Nondirectiveness allows patients to make autonomous decisions without feeling pressured by the counselor.

Question 43: Which DNA repair mechanism corrects single-strand mismatches introduced during replication and is defective in Lynch syndrome?

Mismatch repair (Correct answer)
Base excision repair
Nucleotide excision repair
Homologous recombination

Correct answer: Mismatch repair

Mismatch repair (MMR) corrects replication errors; germline mutations in MMR genes (MLH1, MSH2, MSH6, PMS2) cause Lynch syndrome.

Question 44: Which of the following best describes a de novo mutation?

A mutation that arises newly in the affected individual and is not present in either parent (Correct answer)
A mutation present in all somatic cells but absent from germline
A mutation inherited from a carrier parent
A mutation that reverts to the wild-type sequence

Correct answer: A mutation that arises newly in the affected individual and is not present in either parent

A de novo mutation arises spontaneously in the proband and is not inherited from either parent, often explaining isolated cases of dominant disorders.

Question 45: A patient with a positive cfDNA result for trisomy 18 should be counseled that:

The fetus definitely has trisomy 18
The result confirms the diagnosis and no further testing is needed
Diagnostic confirmation via amniocentesis or CVS is recommended before clinical decisions are made (Correct answer)
The test result is unreliable and should be repeated

Correct answer: Diagnostic confirmation via amniocentesis or CVS is recommended before clinical decisions are made

cfDNA is a screening test, not diagnostic; a positive result requires invasive diagnostic confirmation before clinical management decisions.

Question 46: Lynch syndrome is caused by pathogenic variants in which set of genes?

MLH1, MSH2, MSH6, PMS2, EPCAM (Correct answer)
APC, MUTYH, NTHL1
BRCA1, BRCA2, PALB2
TP53, CHEK2, ATM

Correct answer: MLH1, MSH2, MSH6, PMS2, EPCAM

Lynch syndrome results from germline pathogenic variants in mismatch repair (MMR) genes: MLH1, MSH2, MSH6, PMS2, and EPCAM (which silences MSH2).

Question 47: What CGG repeat size in FMR1 defines a full mutation associated with fragile X syndrome?

5-44 repeats
More than 200 repeats (Correct answer)
55-200 repeats
45-54 repeats

Correct answer: More than 200 repeats

More than 200 CGG repeats typically leads to FMR1 hypermethylation and gene silencing, causing fragile X syndrome.

Question 48: A patient presents at 14 weeks gestation after a CVS revealed trisomy 21 in the fetus. The genetic counselor should provide counseling that includes:

Balanced information about the condition, reproductive options, and support resources (Correct answer)
Only information supporting continuation of the pregnancy
Only information about termination options
A referral to a developmental pediatrician without further discussion

Correct answer: Balanced information about the condition, reproductive options, and support resources

Nondirective counseling requires presenting balanced, comprehensive information about the diagnosis, all options, and available support without bias.

Question 49: Which hereditary syndrome is associated with pathogenic variants in the BRCA1 and BRCA2 genes?

Lynch syndrome
Cowden syndrome
Hereditary breast and ovarian cancer (HBOC) syndrome (Correct answer)
Li-Fraumeni syndrome

Correct answer: Hereditary breast and ovarian cancer (HBOC) syndrome

BRCA1 and BRCA2 pathogenic variants are the hallmark of hereditary breast and ovarian cancer (HBOC) syndrome.

Question 50: Which of the following is a limitation of whole genome sequencing (WGS) compared to targeted panel testing?

WGS has lower sensitivity for detecting SNVs
WGS generates a large number of variants of uncertain significance and incidental findings requiring interpretation (Correct answer)
WGS cannot detect structural variants
WGS requires more DNA input than targeted panels

Correct answer: WGS generates a large number of variants of uncertain significance and incidental findings requiring interpretation

The breadth of WGS results in many VUSs and potential secondary/incidental findings that increase interpretive complexity and counseling burden.

Question 51: In pediatric genetic counseling, assent from a minor patient is BEST described as:

Legally binding consent that replaces parental consent
Not necessary if parents have consented
The child's affirmative agreement to participate in testing, considered alongside parental consent (Correct answer)
Permission obtained only from teenagers aged 16 and older

Correct answer: The child's affirmative agreement to participate in testing, considered alongside parental consent

Assent acknowledges the developing autonomy of minors and is ethically important alongside parental consent, though it is not legally binding.

Question 52: The procedure-related pregnancy loss risk associated with amniocentesis is approximately:

Less than 1 in 5,000
1 in 1,000
1 in 100 to 1 in 200 (Correct answer)
1 in 10

Correct answer: 1 in 100 to 1 in 200

Contemporary studies estimate the procedure-related loss rate for amniocentesis at approximately 1 in 100 to 1 in 200, though older estimates were higher.

Question 53: A pedigree shows an affected father who has no affected sons but all affected daughters. Which inheritance pattern is most likely?

X-linked recessive
X-linked dominant (Correct answer)
Mitochondrial
Y-linked

Correct answer: X-linked dominant

Fathers pass their only X to all daughters and none to sons, so absent male-to-male transmission with all daughters affected indicates X-linked dominant inheritance.

Question 54: Which technology is commonly used in genomic sequencing?

Next-generation sequencing (Correct answer)
Blood pressure monitor
Ultrasound
MRI

Correct answer: Next-generation sequencing

Next-generation sequencing (NGS), also known as high-throughput sequencing, is a revolutionary technology that allows for rapid and cost-effective sequencing of entire genomes or specific regions. It has become the standard method for genomic sequencing due to its ability to generate vast amounts of DNA sequence data simultaneously. Ultrasound and MRI are imaging techniques, and a blood pressure monitor is a diagnostic tool, none of which are used for genomic sequencing.

Question 55: Which pedigree symbol represents a female in genetic counseling?

Triangle
Circle (Correct answer)
Diamond
Square

Correct answer: Circle

In pedigrees, circles are used to represent females.

Question 56: Allelic heterogeneity refers to:

A single variant causing multiple different diseases
Heterozygous variants at the same locus
Different genes causing the same phenotype
Multiple different variants within the same gene causing the same or related phenotypes (Correct answer)

Correct answer: Multiple different variants within the same gene causing the same or related phenotypes

Allelic heterogeneity describes the existence of multiple distinct pathogenic variants within the same gene that all produce the same or similar phenotype.

Question 57: Pharmacogenomics in clinical genetics focuses on:

The pharmacology of genetic testing reagents
How genetic variants influence individual drug metabolism, efficacy, and adverse effects (Correct answer)
Designing new drugs based on genome sequences
Using drugs to treat genetic conditions

Correct answer: How genetic variants influence individual drug metabolism, efficacy, and adverse effects

Pharmacogenomics examines how germline genetic variants (e.g., in CYP450 genes) affect drug response, enabling personalized medication dosing.

Question 58: Peutz-Jeghers syndrome is characterized by hamartomatous polyps and mucocutaneous pigmentation and is caused by variants in:

PTEN
SMAD4
BMPR1A
STK11 (LKB1) (Correct answer)

Correct answer: STK11 (LKB1)

Peutz-Jeghers syndrome is caused by germline STK11 (LKB1) pathogenic variants and is associated with GI hamartomas and elevated cancer risk.

Question 59: Chromosomal microarray analysis (CMA) is MOST appropriate as a first-tier test for:

Patients with a known familial pathogenic single-nucleotide variant
Individuals with intellectual disability, autism spectrum disorder, or multiple congenital anomalies (Correct answer)
Patients with suspected trinucleotide repeat disorders
Carrier screening in couples planning pregnancy

Correct answer: Individuals with intellectual disability, autism spectrum disorder, or multiple congenital anomalies

CMA is recommended as first-tier testing for unexplained intellectual disability, autism, and multiple congenital anomalies due to its high diagnostic yield (~15–20%).

Question 60: Which of the following is an example of the 'empathy' skill in genetic counseling?

Reflecting the patient's emotional state by saying 'This sounds incredibly overwhelming' (Correct answer)
Saying 'I know exactly how you feel'
Offering immediate reassurance that everything will be okay
Changing the subject to reduce patient distress

Correct answer: Reflecting the patient's emotional state by saying 'This sounds incredibly overwhelming'

Empathy involves acknowledging and reflecting the patient's feelings accurately rather than projecting one's own experience or offering premature reassurance.

Question 61: What is the first step in genetic risk assessment?

Conduct a physical examination.
Order genetic testing immediately.
Collect detailed family history. (Correct answer)
Review medical insurance coverage.

Correct answer: Collect detailed family history.

Collecting a comprehensive family history helps identify patterns of inherited conditions.

Question 62: What is the role of chromosomes in genetics?

Store fat
Digest food
Regulate temperature
Transmit DNA to new cells (Correct answer)

Correct answer: Transmit DNA to new cells

Chromosomes are thread-like structures located inside the nucleus of animal and plant cells, made of protein and a single molecule of DNA. Their primary role in genetics is to package and organize DNA, ensuring that genetic information is accurately transmitted to new cells during cell division and from one generation to the next. They carry the genes that determine an individual's traits.

Question 63: Which ethical principle is most directly honored when a counselor presents options without steering the client toward a particular decision?

Justice
Beneficence
Nonmaleficence
Autonomy (Correct answer)

Correct answer: Autonomy

Respecting autonomy means supporting the client's right to make informed, self-determined choices.

Question 64: Which term describes sharing a patient's genetic information without consent?

Gene mapping
Breach of confidentiality (Correct answer)
Genetic literacy
Therapeutic privilege

Correct answer: Breach of confidentiality

Confidentiality is a key ethical obligation, and breaches may have legal consequences.

Question 65: A variant has an allele frequency of 8% in a large general population database. Which ACMG/AMP criterion is most applicable?

PM2, absent from controls
BA1, a stand-alone benign criterion (Correct answer)
PP5, reputable source reports pathogenic
PS3, functional studies show damage

Correct answer: BA1, a stand-alone benign criterion

An allele frequency above 5% is considered stand-alone evidence for a benign classification.

Question 66: Which lifetime breast cancer risk estimate generally triggers consideration of annual breast MRI screening in addition to mammography?

50% or greater
10% or greater
5% or greater
20% or greater (Correct answer)

Correct answer: 20% or greater

ACS and NCCN guidelines recommend supplemental MRI when model-estimated lifetime risk is 20% or higher.

Question 67: In a multifactorial condition like type 2 diabetes, heritability estimates describe:

The proportion of phenotypic variance in a population attributable to genetic factors (Correct answer)
The number of genes involved in disease causation
Whether the condition is dominant or recessive
The probability that a person will develop the condition

Correct answer: The proportion of phenotypic variance in a population attributable to genetic factors

Heritability (h²) is a population statistic representing the fraction of phenotypic variance due to genetic variance, not an individual's risk.

Question 68: Which of the following cancers is part of the Lynch syndrome cancer spectrum?

Mesothelioma
Endometrial, ovarian, gastric, urinary tract, and small bowel cancers (Correct answer)
Pancreatic cancer exclusively
Medullary thyroid cancer

Correct answer: Endometrial, ovarian, gastric, urinary tract, and small bowel cancers

Lynch syndrome increases risk for a broad spectrum including endometrial, ovarian, gastric, urinary tract, small bowel, and other cancers beyond colorectal.

Question 69: Which statement best defines penetrance?

The proportion of individuals with a genotype who show the associated phenotype (Correct answer)
The rate at which new mutations arise per generation
The variability in age of onset within a family
The severity of symptoms in those with a genotype

Correct answer: The proportion of individuals with a genotype who show the associated phenotype

Penetrance is the proportion of individuals with a particular genotype who express the phenotype.

Question 70: A population-based carrier screening program aims to identify which individuals?

Individuals predisposed to late-onset dominant conditions
Only affected individuals in the population
Unaffected individuals who carry one pathogenic variant for a recessive condition and are at reproductive risk (Correct answer)
Newborns with elevated metabolite levels

Correct answer: Unaffected individuals who carry one pathogenic variant for a recessive condition and are at reproductive risk

Carrier screening identifies unaffected heterozygous individuals who are at risk of having affected children when partnered with another carrier.

Question 71: Which PTEN-related syndrome is associated with an increased risk of breast, thyroid, endometrial, and colorectal cancers along with macrocephaly?

Juvenile polyposis syndrome
Cowden syndrome (PTEN hamartoma tumor syndrome) (Correct answer)
Peutz-Jeghers syndrome
Bannayan-Riley-Ruvalcaba syndrome

Correct answer: Cowden syndrome (PTEN hamartoma tumor syndrome)

Cowden syndrome, caused by germline PTEN pathogenic variants, presents with multiple hamartomas, macrocephaly, and elevated risks for breast, thyroid, and endometrial cancers.

Question 72: Which of the following epigenetic modifications most directly contributes to gene silencing by adding a chemical group to cytosine residues in CpG islands?

DNA methylation (Correct answer)
Chromatin remodeling via SWI/SNF
Histone phosphorylation
Histone acetylation

Correct answer: DNA methylation

DNA methylation at CpG islands, catalyzed by DNA methyltransferases, is strongly associated with transcriptional silencing of the associated gene.

Question 73: Which of the following describes 'pleiotropy'?

A gene expressed differently in males versus females
One gene locus affected by multiple different variants
Multiple genes each contributing a small effect to one trait
A single gene that influences multiple phenotypic traits or organ systems (Correct answer)

Correct answer: A single gene that influences multiple phenotypic traits or organ systems

Pleiotropy refers to one gene having effects on multiple, seemingly unrelated phenotypic traits or organ systems.

Question 74: A genetic counselor is writing a patient letter after a variant of uncertain significance (VUS) result. The letter should primarily:

Recommend immediate prophylactic surgery
State that the result is likely pathogenic for future planning
Explain what a VUS means and emphasize the need for reclassification follow-up (Correct answer)
Reassure the patient the result is normal

Correct answer: Explain what a VUS means and emphasize the need for reclassification follow-up

A VUS letter must clearly define the uncertain nature of the result and establish a plan for monitoring reclassification updates.

Question 75: Which of the following is NOT a standard ACMG/AMP variant classification category?

Likely deleterious (Correct answer)
Likely benign
Likely pathogenic
Variant of uncertain significance

Correct answer: Likely deleterious

The five ACMG/AMP tiers are pathogenic, likely pathogenic, VUS, likely benign, and benign.

Question 76: Chorionic villus sampling (CVS) is typically performed at which gestational age?

22–24 weeks
15–20 weeks
10–13 weeks (Correct answer)
After 28 weeks

Correct answer: 10–13 weeks

CVS is performed in the first trimester between 10 and 13 weeks, providing earlier diagnostic results compared to amniocentesis.

Question 77: Which approach is most consistent with nondirectiveness in prenatal counseling?

Refusing to discuss options the counselor disagrees with
Providing balanced information and exploring the client's own values (Correct answer)
Telling the client what most patients choose
Recommending termination when a trisomy is found

Correct answer: Providing balanced information and exploring the client's own values

Nondirective counseling gives accurate, balanced information and supports the client's values-based decision.

Question 78: A genetic counselor explains that a condition has a population prevalence of 1 in 10,000. Using Hardy-Weinberg, the carrier frequency is approximately:

1 in 10,000
1 in 200
1 in 100
1 in 50 (Correct answer)

Correct answer: 1 in 50

For q² = 1/10,000, q = 1/100; carrier frequency 2pq ≈ 2q = 1/50, since p ≈ 1 for rare recessive conditions.

Question 79: Which of the following best describes 'variant of uncertain significance' (VUS) in the context of cancer genetics?

A variant whose clinical significance for disease risk has not yet been established (Correct answer)
A variant that is too rare to analyze
A variant known to cause cancer in all carriers
A variant that is definitely benign but still reported

Correct answer: A variant whose clinical significance for disease risk has not yet been established

A VUS has insufficient evidence to classify it as pathogenic or benign and should not be used to guide clinical management decisions.

Question 80: Which communication technique is most effective when disclosing a pathogenic variant result to a patient?

Use technical jargon to demonstrate expertise
Avoid emotional language entirely
Provide all information at once to be efficient
Deliver information in small chunks with pauses to check understanding (Correct answer)

Correct answer: Deliver information in small chunks with pauses to check understanding

Chunking information and checking understanding allows patients to process difficult news more effectively.

Question 81: An unaffected relative is being considered for predictive testing based on a family member's VUS. What is the correct approach?

Do not use the VUS for clinical decisions; manage by personal and family history (Correct answer)
Treat the relative as high risk and begin surveillance
Reassure the relative that the variant is benign
Offer prophylactic surgery to carriers of the VUS

Correct answer: Do not use the VUS for clinical decisions; manage by personal and family history

A VUS should not drive clinical management or cascade testing, and care should follow history-based risk.

Question 82: Which condition is typically associated with autosomal recessive inheritance?

Neurofibromatosis type 1
Cystic fibrosis (Correct answer)
Huntington's disease
Marfan syndrome

Correct answer: Cystic fibrosis

Cystic fibrosis is a classic example of an autosomal recessive condition.

Question 83: A patient asks about the difference between a 'screen positive' and a 'diagnostic positive' result for Down syndrome. The counselor correctly explains that:

Both terms mean the same thing clinically
Screen positives are used only for research purposes
A diagnostic positive is less reliable than a screen positive
A screen positive indicates increased risk but requires diagnostic confirmation; a diagnostic positive confirms the diagnosis (Correct answer)

Correct answer: A screen positive indicates increased risk but requires diagnostic confirmation; a diagnostic positive confirms the diagnosis

Screening identifies individuals at increased risk who need diagnostic testing, while diagnostic testing provides definitive chromosomal confirmation.

Question 84: What is a limitation of direct-to-consumer genetic tests?

They are free for all users
They may lack clinical accuracy (Correct answer)
They require surgery
They are reviewed by doctors only

Correct answer: They may lack clinical accuracy

A significant limitation of direct-to-consumer (DTC) genetic tests is that they may lack the rigorous clinical accuracy and validation of tests ordered through a healthcare provider. These tests might not cover all relevant genes, may report variants of uncertain significance without proper clinical context, or provide results that are not actionable or fully understood without professional interpretation. This can lead to misinterpretation, unnecessary anxiety, or false reassurance for consumers.

Question 85: A mosaic pathogenic variant found in an individual means:

The pathogenic variant is present in some cells but not all cells of the individual (Correct answer)
The variant was inherited from both parents
Two different pathogenic variants are present in the same gene
The variant is present in a pseudogene

Correct answer: The pathogenic variant is present in some cells but not all cells of the individual

Mosaicism occurs when a variant arises post-zygotically, resulting in two or more cell populations with different genotypes within the same individual.

Question 86: Hardy-Weinberg equilibrium requires which of the following conditions?

Positive selection for advantageous alleles
Random mating, no mutation, no migration, no selection, and large population size (Correct answer)
High rates of consanguinity
Small population size with genetic drift

Correct answer: Random mating, no mutation, no migration, no selection, and large population size

Hardy-Weinberg equilibrium is maintained in large, randomly mating populations free of mutation, migration, and selection pressure.

Question 87: The concept of 'heterozygote advantage' explains the persistence of cystic fibrosis alleles in European populations through the hypothesis that:

Natural selection has no effect on CF allele frequencies
CF carriers may have had increased resistance to certain infectious diseases such as cholera (Correct answer)
The CF allele mutates frequently from normal alleles
CF carriers have a higher reproductive rate by chance

Correct answer: CF carriers may have had increased resistance to certain infectious diseases such as cholera

One hypothesis for the persistence of CFTR variants is that carriers may have had a survival advantage against chloride-depleting infections like cholera.

Question 88: Which counseling approach focuses on exploring and resolving ambivalence about genetic testing decisions?

Psychodynamic counseling
Cognitive-behavioral therapy
Exposure therapy
Motivational interviewing (Correct answer)

Correct answer: Motivational interviewing

Motivational interviewing is designed to help patients explore ambivalence and strengthen their own motivation toward a decision.

Question 89: Which term describes the increased frequency of a condition in offspring of consanguineous couples compared with the general population?

Heterozygote advantage
Pleiotropy
Penetrance
Autozygosity (Correct answer)

Correct answer: Autozygosity

Autozygosity refers to inheriting identical-by-descent alleles from a common ancestor, which increases the risk of homozygosity for recessive pathogenic variants in consanguineous offspring.

Question 90: When counseling a couple for whom one partner is a carrier of an X-linked recessive condition, which reproductive outcome is CORRECT?

All daughters will be affected
All sons will be affected
50% of sons will be affected and 50% of daughters will be carriers (Correct answer)
25% of all children will be affected

Correct answer: 50% of sons will be affected and 50% of daughters will be carriers

For X-linked recessive conditions, carrier mothers pass the variant to 50% of sons (who are affected) and 50% of daughters (who are carriers).

Question 91: Fluorescence in situ hybridization (FISH) is BEST used in clinical genetics to:

Perform genome-wide copy number analysis
Sequence specific gene regions
Detect specific chromosomal deletions, duplications, or rearrangements using targeted probes (Correct answer)
Identify single-nucleotide variants

Correct answer: Detect specific chromosomal deletions, duplications, or rearrangements using targeted probes

FISH uses fluorescently labeled probes complementary to specific chromosomal regions to detect targeted deletions, duplications, or translocations.

Question 92: Which of the following describes a mutation?

A temporary fever
A change in the DNA sequence (Correct answer)
An immune response
A protein made by the body

Correct answer: A change in the DNA sequence

A mutation is defined as a change in the DNA sequence of an organism. These changes can range from a single nucleotide alteration to large-scale chromosomal rearrangements. Mutations can occur spontaneously or be induced by external factors, and they are the ultimate source of genetic variation, sometimes leading to disease or providing evolutionary advantage.

Question 93: What is consanguinity in genetic counseling?

Mismatched blood types
Biological relationship between partners (Correct answer)
Genetic counseling over the phone
Adopted family relationships

Correct answer: Biological relationship between partners

Consanguinity refers to parents who are biologically related, increasing genetic risks.

Question 94: How many pairs of chromosomes are typically found in human cells?

22
20
46
23 (Correct answer)

Correct answer: 23

Human cells typically contain 23 pairs of chromosomes, totaling 46 chromosomes. Of these, 22 pairs are autosomes (non-sex chromosomes), and one pair consists of sex chromosomes (XX for females, XY for males). This number is characteristic for the human species.

Question 95: Chromosomal microarray analysis (CMA) in the prenatal setting has advantages over karyotype because it can detect:

Only larger chromosomal deletions
Single-gene variants
Trinucleotide repeat expansions
Submicroscopic copy number variants (CNVs) not visible by standard karyotype (Correct answer)

Correct answer: Submicroscopic copy number variants (CNVs) not visible by standard karyotype

CMA detects small CNVs (deletions and duplications) at a higher resolution than karyotype but does not detect single-nucleotide variants or repeat expansions.

Question 96: Which statement best defines penetrance?

The proportion of individuals with a disease-causing genotype who show the phenotype (Correct answer)
The degree of severity of a phenotype in an affected individual
The number of different phenotypes caused by one gene
The rate at which new mutations arise

Correct answer: The proportion of individuals with a disease-causing genotype who show the phenotype

Penetrance is the percentage of individuals with a given genotype who exhibit the associated phenotype, whereas expressivity refers to severity.

Question 97: A patient is found to have a fetus with a de novo pathogenic variant identified on exome sequencing. 'De novo' means:

The variant was inherited from the father
The variant is of uncertain significance
The variant was inherited from the mother
The variant arose newly in the fetus and is not present in either parent (Correct answer)

Correct answer: The variant arose newly in the fetus and is not present in either parent

De novo variants arise spontaneously in the germline or early development and are absent in both biological parents.

Question 98: What is the main purpose of genomic testing?

To assess dietary preferences
To identify disease-related genetic variants (Correct answer)
To measure cholesterol levels
To determine eye color

Correct answer: To identify disease-related genetic variants

Genomic testing identifies genetic variants that may contribute to disease or inherited traits.

Question 99: Penetrance in genetics refers to:

The severity of disease in affected individuals
The number of genes responsible for a condition
The proportion of individuals with a given genotype who exhibit the associated phenotype (Correct answer)
The age at which a genetic condition first appears

Correct answer: The proportion of individuals with a given genotype who exhibit the associated phenotype

Penetrance is the proportion of individuals with a pathogenic genotype who show clinical features; incomplete penetrance means not all carriers are affected.

Question 100: The recurrence risk for a multifactorial condition in a sibling of an affected individual is BEST approximated by:

100% for identical twins
50% regardless of prevalence
The square root of the population prevalence (Correct answer)
25% (same as autosomal recessive)

Correct answer: The square root of the population prevalence

For multifactorial conditions, the empiric recurrence risk in first-degree relatives is approximately the square root of the population prevalence.

Question 101: A patient declines recommended genetic testing. The genetic counselor's BEST response is to:

Encourage the patient to reconsider by emphasizing the benefits
Respect the decision, document it, and leave the door open for future discussion (Correct answer)
Refer the patient to another provider who may be more persuasive
Request an ethics consultation

Correct answer: Respect the decision, document it, and leave the door open for future discussion

Patient autonomy includes the right to decline testing; the counselor should respect the decision and ensure the patient knows they can revisit it.

Question 102: During meiosis I, homologous chromosomes exchange segments in a process called:

Independent assortment
Crossing over (recombination) (Correct answer)
Sister chromatid exchange
Non-disjunction

Correct answer: Crossing over (recombination)

Crossing over (recombination) occurs during prophase I of meiosis when homologous chromosomes exchange corresponding segments, generating genetic diversity.

Question 103: Which concept best explains the variable severity of mitochondrial disease among maternally related family members?

Anticipation
Genomic imprinting
Uniparental disomy
Heteroplasmy (Correct answer)

Correct answer: Heteroplasmy

Heteroplasmy is the mix of mutant and normal mtDNA, and the proportion varies between cells and individuals, producing variable severity.

Question 104: A patient with Li-Fraumeni syndrome carries a germline TP53 pathogenic variant. Which of the following cancer surveillance recommendations is MOST appropriate?

Colonoscopy every 3 years starting at age 25
No surveillance needed until symptoms arise
Annual mammography starting at age 40 only
Whole-body MRI annually, with brain MRI and breast MRI included (Correct answer)

Correct answer: Whole-body MRI annually, with brain MRI and breast MRI included

Whole-body MRI is the primary surveillance tool for Li-Fraumeni syndrome due to the broad spectrum of associated cancers.

Question 105: Which measure of disease frequency represents the proportion of a population affected with a condition at a specific point in time?

Incidence
Cumulative incidence
Attributable risk
Point prevalence (Correct answer)

Correct answer: Point prevalence

Point prevalence measures the proportion of individuals in a population who have a condition at a specific moment in time.

Question 106: A 28-year-old woman is referred after her mother was diagnosed with ovarian cancer. BRCA1/2 testing is BEST initiated with:

The patient's siblings simultaneously
The affected mother first to identify the familial variant before testing unaffected relatives (Correct answer)
The 28-year-old patient directly since she is at risk
Population-based BRCA testing without family history context

Correct answer: The affected mother first to identify the familial variant before testing unaffected relatives

Testing the affected individual first is optimal to identify the specific familial variant; if none is found, uninformative results in unaffected relatives are less meaningful.

Question 107: Why is the proband important in risk assessment?

They initiate the family health analysis. (Correct answer)
They are the oldest family member.
They are the counselor's assistant.
They represent non-biological family.

Correct answer: They initiate the family health analysis.

The proband is the starting point for analyzing the family's genetic history.

Question 108: In the context of trinucleotide repeat expansion disorders, which mechanism best explains the phenomenon of anticipation?

Somatic mosaicism increases in severity with each generation
Epigenetic silencing accumulates over generations reducing gene expression
Repeat sequences become unstable and tend to expand further with each successive transmission (Correct answer)
Increased penetrance in successive generations due to environmental factors

Correct answer: Repeat sequences become unstable and tend to expand further with each successive transmission

Trinucleotide repeat tracts are meiotically unstable and tend to expand during transmission, leading to progressively larger repeats and earlier/more severe disease in successive generations.

Question 109: Whole exome sequencing (WES) sequences:

Mitochondrial DNA exclusively
All protein-coding exons, approximately 1–2% of the genome (Correct answer)
The entire genome including intergenic regions
Only known disease-causing genes

Correct answer: All protein-coding exons, approximately 1–2% of the genome

WES captures and sequences the coding exons of all known genes, representing approximately 1–2% of the total genome but containing ~85% of known disease-causing variants.

Question 110: The American College of Medical Genetics (ACMG) recommends that clinical laboratories report secondary findings in a defined list of genes. These findings are BEST described as:

Variants associated with pharmacogenomics
Variants found incidentally that are unrelated to the reason for testing but have actionable health implications (Correct answer)
Variants that are benign but of scientific interest
All variants of uncertain significance found during sequencing

Correct answer: Variants found incidentally that are unrelated to the reason for testing but have actionable health implications

ACMG secondary findings are medically actionable variants in a specific gene list found incidentally during sequencing that patients may opt in or out of receiving.

Question 111: The 'teach-back' method is used in genetic counseling to:

Review previously covered session material
Train the counselor on new techniques
Verify that the patient has understood the information provided (Correct answer)
Teach patients how to counsel family members

Correct answer: Verify that the patient has understood the information provided

Teach-back confirms comprehension by asking patients to explain information back in their own words.

Question 112: The quad screen (maternal serum analytes) is a second-trimester screening test that includes which analytes?

AFP, hCG, unconjugated estriol, and inhibin A (Correct answer)
AFP, hCG, PAPP-A, and inhibin A
AFP, hCG, PAPP-A, and NT
AFP, unconjugated estriol, PAPP-A, and inhibin A

Correct answer: AFP, hCG, unconjugated estriol, and inhibin A

The quad screen measures AFP, hCG, unconjugated estriol (uE3), and inhibin A to screen for trisomies 21, 18, and neural tube defects.

Question 113: Approximately what percentage of individuals with Down syndrome have free trisomy 21 due to meiotic nondisjunction?

75%
50%
99.9%
95% (Correct answer)

Correct answer: 95%

About 95% of Down syndrome cases are free trisomy 21, with the remainder due to translocations and mosaicism.

Question 114: The Amsterdam II criteria are used to identify families at high risk for:

Lynch syndrome (Correct answer)
Familial adenomatous polyposis
Li-Fraumeni syndrome
HBOC syndrome

Correct answer: Lynch syndrome

The Amsterdam II criteria identify families with increased risk for Lynch syndrome based on colorectal cancer and Lynch-spectrum cancers across generations.

Question 115: When both members of a couple are carriers for an autosomal recessive condition, the recurrence risk with each pregnancy is:

25% (Correct answer)
100%
75%
50%

Correct answer: 25%

When both parents are carriers for an autosomal recessive condition, each pregnancy has a 25% chance of being affected.

Question 116: What is gene expression?

DNA packaging
Process of making protein from a gene (Correct answer)
Turning genes into sugar
Gene duplication

Correct answer: Process of making protein from a gene

Gene expression is the fundamental process by which information from a gene is used in the synthesis of a functional gene product, such as a protein or a functional RNA molecule. This process involves transcription (DNA to RNA) and translation (RNA to protein), ultimately allowing the genetic instructions to manifest as observable traits or cellular functions.

Question 117: Which test is most appropriate to detect a balanced reciprocal translocation in a couple with recurrent pregnancy loss?

Whole exome sequencing
Karyotype (Correct answer)
Methylation analysis
Chromosomal microarray

Correct answer: Karyotype

Karyotype visualizes balanced rearrangements, which microarray cannot detect because there is no net gain or loss of material.

Question 118: What does exome sequencing analyze?

Non-coding RNA
All regulatory sequences
Only mitochondrial DNA
The coding regions of the genome (Correct answer)

Correct answer: The coding regions of the genome

Exome sequencing specifically analyzes the exome, which comprises all the protein-coding regions of the genome (exons). While the exome makes up only about 1-2% of the entire genome, it contains the vast majority of known disease-causing mutations. This targeted approach is efficient for identifying genetic causes of many Mendelian disorders.

Question 119: What is the human genome?

An enzyme in digestion
A medical textbook
A blood type classification
All the chromosomes in a human (Correct answer)

Correct answer: All the chromosomes in a human

The human genome refers to the complete set of genetic instructions found in a human cell, encompassing all the DNA contained within the 23 pairs of chromosomes in the nucleus and the small circular DNA in the mitochondria. It contains all the information needed to build and maintain a human being. It is not a textbook, blood classification, or enzyme.

Question 120: A client with a newly diagnosed hereditary condition reports guilt about possibly passing it on to children. Which concept best describes this reaction?

Genetic determinism
Therapeutic misconception
Survivor guilt or transmission guilt (Correct answer)
Anticipatory loss only

Correct answer: Survivor guilt or transmission guilt

Guilt over transmitting a genetic condition is a common psychosocial response that counselors should normalize and explore.

Question 121: Uniparental disomy (UPD) occurs when:

Two chromosomes exchange segments during recombination
A segment of a chromosome is deleted and replaced by the other parental copy
Both copies of a chromosome pair are inherited from the same parent (Correct answer)
An individual inherits an extra copy of a chromosome from one parent

Correct answer: Both copies of a chromosome pair are inherited from the same parent

UPD occurs when both homologs of a chromosome pair are derived from one parent rather than one from each parent, potentially revealing imprinting disorders or recessive conditions.

Question 122: In the context of genetic counseling, 'nondirectiveness' primarily means the counselor should:

Always present options neutrally without any guidance
Refuse to give any recommendations
Support client autonomy without imposing the counselor's values (Correct answer)
Avoid discussing the emotional aspects of a diagnosis

Correct answer: Support client autonomy without imposing the counselor's values

Nondirectiveness means supporting patient autonomy and self-determination rather than directing patients toward specific choices.

Question 123: Which of the following BEST describes the purpose of a pedigree in a genetic counseling session?

To visually map family medical history and identify inheritance patterns (Correct answer)
To replace the need for genetic testing
To provide patients with a record of their relatives
To satisfy documentation requirements only

Correct answer: To visually map family medical history and identify inheritance patterns

Pedigrees systematically capture multigenerational family history to analyze inheritance patterns and identify at-risk relatives.

Question 124: Which of the following increases the accuracy of a genetic risk assessment?

Only the proband's medical history
Three-generation pedigree with diagnosis details (Correct answer)
Zodiac signs of family members
Medical history of family pets

Correct answer: Three-generation pedigree with diagnosis details

Accurate risk assessments depend on three-generation family histories with health details.

Question 125: A nuchal translucency (NT) measurement of ≥3.5 mm at 11–14 weeks is associated with increased risk for:

Premature labor exclusively
Neural tube defects and Down syndrome only
Chromosomal abnormalities and structural defects including cardiac anomalies (Correct answer)
Neural tube defects only

Correct answer: Chromosomal abnormalities and structural defects including cardiac anomalies

An increased NT is associated with a broad spectrum of chromosomal aneuploidies, structural anomalies, and genetic syndromes.

Question 126: A patient with a known BRCA2 pathogenic variant asks about male-specific cancer risks. The counselor should inform him that BRCA2 increases his risk for:

Prostate cancer and male breast cancer (Correct answer)
No male-specific cancers
Testicular cancer only
Bladder cancer only

Correct answer: Prostate cancer and male breast cancer

BRCA2 carriers have elevated risks for prostate cancer and male breast cancer, making surveillance important for male carriers.

Question 127: A woman with a pathogenic BRCA1 variant asks about risk-reducing options. Which of the following has the greatest evidence for reducing ovarian cancer mortality?

Annual CA-125 and transvaginal ultrasound
Prophylactic whole-abdominal radiation
Risk-reducing salpingo-oophorectomy (RRSO) (Correct answer)
Oral contraceptive use indefinitely

Correct answer: Risk-reducing salpingo-oophorectomy (RRSO)

RRSO is the most effective intervention for reducing ovarian cancer risk and mortality in BRCA1 carriers, typically recommended between ages 35–40.

Question 128: A variant has a relative risk of 2.0 for a disease with a 12% baseline lifetime risk. What is the approximate absolute lifetime risk for a variant carrier?

20%
14%
48%
24% (Correct answer)

Correct answer: 24%

Multiplying the baseline risk by the relative risk gives about 24%.

Question 129: A parent asks to have a healthy 8-year-old tested for adult-onset Huntington disease. According to professional guidelines, what is the best recommendation?

Test now so the family can plan
Test only if the child agrees verbally
Defer testing until the child is an adult and can decide for themself (Correct answer)
Test using a research laboratory to avoid medical records

Correct answer: Defer testing until the child is an adult and can decide for themself

Predictive testing for adult-onset conditions without childhood medical benefit should generally be deferred to preserve the child's future autonomy.

Question 130: Which of the following is a characteristic feature of hereditary diffuse gastric cancer (HDGC) syndrome?

Multiple colonic polyps
Hamartomatous polyps of the GI tract
Pathogenic variants in SMAD4
Germline CDH1 pathogenic variants and lobular breast cancer risk (Correct answer)

Correct answer: Germline CDH1 pathogenic variants and lobular breast cancer risk

HDGC is caused by CDH1 germline pathogenic variants and confers high risks for diffuse gastric cancer and lobular breast cancer.

Question 131: What is the purpose of informed consent in genetic counseling?

To collect insurance details
To gather demographic data
To authorize genetic testing with full understanding (Correct answer)
To expedite treatment decisions

Correct answer: To authorize genetic testing with full understanding

Informed consent ensures patients understand the benefits, risks, and limitations before testing.

Question 132: Which law protects individuals from genetic discrimination in the U.S.?

GINA (Correct answer)
ADA
FERPA
HIPAA

Correct answer: GINA

The Genetic Information Nondiscrimination Act (GINA) prohibits misuse of genetic information.

Question 133: Genomic imprinting results in conditions where disease expression depends on:

The age of onset of the condition
The number of copies of the gene present
The sex of the affected individual
Whether the pathogenic variant was inherited from the mother or father (Correct answer)

Correct answer: Whether the pathogenic variant was inherited from the mother or father

Genomic imprinting silences one parental allele depending on its parental origin, so the phenotype depends on whether the variant came from the mother or father.

Question 134: What is the purpose of using a risk calculator in genetic counseling?

To assess insurance premiums
To record diet history
To predict career paths
To calculate genetic risk probabilities (Correct answer)

Correct answer: To calculate genetic risk probabilities

Risk calculators help quantify the likelihood of passing on or developing a genetic condition.

Question 135: In the context of clinical molecular testing, 'sensitivity' is defined as:

The probability that a positive test result is a true positive
The proportion of true negatives correctly identified by the test
The proportion of variants correctly classified as benign
The proportion of true positives correctly identified by the test (Correct answer)

Correct answer: The proportion of true positives correctly identified by the test

Sensitivity measures the test's ability to correctly identify affected individuals (true positive rate), while specificity measures the correct identification of unaffected individuals.

Question 136: Preimplantation genetic testing for monogenic conditions (PGT-M) requires which INITIAL step?

Completing two rounds of IVF before analysis
Submitting a referral to a reproductive endocrinologist
Identifying the specific familial pathogenic variant through proband testing (Correct answer)
Confirming the couple's carrier status via blood draw

Correct answer: Identifying the specific familial pathogenic variant through proband testing

PGT-M requires knowledge of the exact familial variant so the laboratory can design a specific probe or analysis strategy for the embryo.

Question 137: When presenting recurrence risk statistics to a patient, which format is generally MOST effective for understanding?

Natural frequencies (e.g., 1 in 4 chance) (Correct answer)
Odds ratios (e.g., 3:1)
Percentages only (e.g., 25%)
Verbal descriptions only (e.g., 'low risk')

Correct answer: Natural frequencies (e.g., 1 in 4 chance)

Research shows patients understand and accurately recall risk information better when presented as natural frequencies rather than percentages or odds.

Question 138: Why is family history still relevant with genomic testing?

It confirms lab techniques
It is only useful for ancestry
It replaces the need for testing
It helps personalize interpretation (Correct answer)

Correct answer: It helps personalize interpretation

Family history is crucial even with genomic testing because it provides essential context for interpreting genetic results. It helps identify patterns of inheritance, highlight specific genes or conditions to investigate, and assess the clinical significance of variants found. This personalization ensures that genetic findings are understood within the individual's broader health and familial background, guiding appropriate management and counseling.

Question 139: A patient with limited health literacy is seen for BRCA testing counseling. The BEST approach is to:

Refer the patient to a specialist in health literacy
Simplify explanations and use visual aids to confirm understanding (Correct answer)
Postpone counseling until literacy improves
Use the same materials as with all patients

Correct answer: Simplify explanations and use visual aids to confirm understanding

Adapting communication with plain language and visual aids ensures informed consent and comprehension regardless of literacy level.

Question 140: The Bethesda guidelines for colorectal cancer testing were designed to identify tumors likely to show:

BRAF V600E mutations
HER2 amplification
KRAS mutations
Microsatellite instability (MSI) (Correct answer)

Correct answer: Microsatellite instability (MSI)

The Bethesda guidelines identify colorectal cancers with features suggesting MSI, prompting further Lynch syndrome evaluation.

Question 141: A woman has a 1/2 prior risk of carrying an X-linked recessive condition and has two unaffected sons. What is her posterior carrier risk by Bayesian analysis?

1/2
1/8
1/5 (Correct answer)
1/4

Correct answer: 1/5

Joint carrier probability 1/8 divided by (1/8 + 1/2) equals 1/5.

Question 142: What is the most common molecular mechanism underlying Prader-Willi syndrome?

Maternal 15q11-q13 deletion
Paternal UBE3A mutation
Paternal 15q11-q13 deletion (Correct answer)
Trisomy 15 rescue with paternal UPD only

Correct answer: Paternal 15q11-q13 deletion

About 70% of Prader-Willi cases result from a de novo deletion of the paternally inherited 15q11-q13 region.

Question 143: A client's adult sister asks the counselor for the client's BRCA1 result, but the client has not consented to disclosure. What is the most appropriate response?

Decline to disclose and encourage the client to share the result with family (Correct answer)
Share the result because it affects the sister's cancer risk
Mail the report to the sister after one week
Share only that the result was abnormal

Correct answer: Decline to disclose and encourage the client to share the result with family

Confidentiality belongs to the client, so the counselor should not disclose without consent but can encourage and support family communication.

Question 144: Which organelle contains its own DNA?

Mitochondrion (Correct answer)
Ribosome
Nucleus
Endoplasmic reticulum

Correct answer: Mitochondrion

The mitochondrion is a unique organelle within eukaryotic cells that contains its own small, circular DNA molecule, separate from the nuclear DNA. This mitochondrial DNA (mtDNA) encodes for some proteins involved in cellular respiration and is inherited exclusively from the mother. The nucleus also contains DNA, but the question asks for an organelle that contains *its own* DNA, distinct from the main nuclear genome.

Question 145: Cell-free DNA (cfDNA) screening in pregnancy MOST accurately screens for which condition?

Single-gene disorders such as cystic fibrosis
Trisomy 21 (Down syndrome) (Correct answer)
Structural heart defects
Neural tube defects

Correct answer: Trisomy 21 (Down syndrome)

cfDNA screening has the highest sensitivity and specificity for trisomy 21 among common chromosomal aneuploidies.

Question 146: The ACMG/AMP criterion PVS1 applies to which type of variant?

A null variant in a gene where loss of function is a known disease mechanism (Correct answer)
A variant seen in many unaffected controls
Any missense variant in a conserved domain
A synonymous variant predicted to alter splicing

Correct answer: A null variant in a gene where loss of function is a known disease mechanism

PVS1 is very strong evidence for nonsense, frameshift, canonical splice-site, or similar null variants in LOF-mechanism genes.

Question 147: Which evidence criterion is classified as 'very strong pathogenic' (PVS1) in ACMG/AMP variant interpretation?

Functional studies demonstrate a damaging effect
The variant is observed in multiple unrelated affected individuals
The variant is absent from population databases
Null variant (nonsense, frameshift, canonical splice site) in a gene where loss of function is a known disease mechanism (Correct answer)

Correct answer: Null variant (nonsense, frameshift, canonical splice site) in a gene where loss of function is a known disease mechanism

PVS1 is assigned to null variants (loss-of-function) in genes where haploinsufficiency or loss-of-function is an established disease mechanism.

Question 148: What is a potential psychosocial response to genetic testing results?

Increased appetite
Anxiety (Correct answer)
Increased sleep duration
Euphoria

Correct answer: Anxiety

Anxiety is a common emotional reaction to receiving genetic risk or diagnosis information.

Question 149: Genetic drift is MOST significant in:

Populations experiencing strong positive selection
Large, outbred populations
Small, isolated populations (Correct answer)
Populations with high mutation rates

Correct answer: Small, isolated populations

Genetic drift causes random fluctuation in allele frequencies that is most pronounced in small populations where chance events have a larger proportional impact.

Question 150: Multiple endocrine neoplasia type 2 (MEN2) is caused by germline pathogenic variants in which gene?

VHL
RET (Correct answer)
SDHA
NF1

Correct answer: RET

MEN2 is caused by activating germline variants in the RET proto-oncogene and is associated with medullary thyroid cancer, pheochromocytoma, and hyperparathyroidism.

Question 151: A laboratory reports a deletion using the term 'copy number variant (CNV).' This means:

A segment of DNA has been duplicated or deleted relative to the reference genome (Correct answer)
A single nucleotide has been changed
A chromosomal translocation has occurred
Two different genes have been fused

Correct answer: A segment of DNA has been duplicated or deleted relative to the reference genome

CNVs are structural variants involving gains (duplications) or losses (deletions) of genomic segments ranging from kilobases to megabases.

Question 152: A patient has a personal history of colorectal cancer at age 38 with MSI-high tumor testing. This MOST likely suggests:

Familial adenomatous polyposis (FAP)
Serrated polyposis syndrome
Lynch syndrome (Correct answer)
MUTYH-associated polyposis (MAP)

Correct answer: Lynch syndrome

Early-onset colorectal cancer with MSI-high tumor testing is a classic presentation prompting evaluation for Lynch syndrome.

Question 153: Which factor may influence a person's decision to undergo genetic testing?

Cultural beliefs (Correct answer)
Brand of test kit
Color of medical forms
TV advertisements

Correct answer: Cultural beliefs

Cultural beliefs can shape attitudes toward testing, privacy, and disease perception.

Question 154: A missense variant is confirmed de novo in a child with a consistent phenotype, with maternity and paternity confirmed. What ACMG/AMP evidence does this support?

PP4, a supporting phenotype criterion only
BS2, a strong benign criterion
BP5, a supporting benign criterion
PS2, a strong pathogenic criterion (Correct answer)

Correct answer: PS2, a strong pathogenic criterion

A confirmed de novo variant with a matching phenotype supports pathogenicity, with PS2 requiring confirmed parentage.

Question 155: The phenomenon of 'anticipation' in cancer genetics refers to:

Earlier age of cancer onset in a patient who is anxious about their diagnosis
The expectation that all carriers will develop cancer
Physicians anticipating a positive genetic test result before testing
Earlier onset or increased severity of a condition in successive generations due to expanding repeats (Correct answer)

Correct answer: Earlier onset or increased severity of a condition in successive generations due to expanding repeats

Anticipation describes the observation in certain conditions where repeat expansions grow across generations, causing earlier onset or greater severity.

Question 156: Tumor testing for microsatellite instability (MSI) or mismatch repair (MMR) protein expression via immunohistochemistry (IHC) is recommended for:

All patients diagnosed with colorectal cancer (Correct answer)
Patients over age 70 with any cancer
Patients with no family history of cancer
All patients with breast cancer

Correct answer: All patients diagnosed with colorectal cancer

Universal tumor testing for MSI/MMR is recommended for all colorectal cancer patients to identify those who may have Lynch syndrome.

Question 157: Which type of mutation involves the insertion of one or two nucleotides, causing a shift in the reading frame of downstream codons?

Frameshift mutation (Correct answer)
Missense mutation
Silent mutation
Nonsense mutation

Correct answer: Frameshift mutation

A frameshift mutation results from insertion or deletion of nucleotides in a number not divisible by three, altering every codon downstream of the mutation.

Question 158: Preimplantation genetic testing for aneuploidy (PGT-A) is used to:

Diagnose chromosomal abnormalities in an ongoing pregnancy
Replace the need for prenatal diagnosis
Predict the sex of a naturally conceived fetus
Screen embryos created through IVF for chromosomal abnormalities before transfer (Correct answer)

Correct answer: Screen embryos created through IVF for chromosomal abnormalities before transfer

PGT-A screens IVF embryos for aneuploidy prior to uterine transfer to improve implantation success and reduce miscarriage risk.

Question 159: Under the ClinGen SVI recommendations, how is the PM2 criterion (absent or extremely rare in population databases) now generally applied?

Only when homozygotes are observed
As a stand-alone benign criterion
At very strong strength
At supporting strength (Correct answer)

Correct answer: At supporting strength

ClinGen SVI recommended downgrading PM2 from moderate to supporting strength.

Question 160: Which condition is commonly inherited in an autosomal dominant pattern?

Sickle cell anemia
Marfan syndrome (Correct answer)
Phenylketonuria
Cystic fibrosis

Correct answer: Marfan syndrome

Marfan syndrome is a classic example of a condition inherited in an autosomal dominant pattern. This means that only one copy of the mutated gene (FBN1) is sufficient to cause the disorder. Affected individuals have a 50% chance of passing the condition to each of their children, regardless of the child's sex.

Question 161: Which informed consent element is MOST critical when discussing predictive genetic testing for a late-onset condition?

The potential psychological impact of knowing one's genetic status (Correct answer)
The number of labs that offer the test
The time required to complete the test
The cost of the genetic test

Correct answer: The potential psychological impact of knowing one's genetic status

Predictive testing for late-onset conditions has significant psychological implications that must be addressed as part of informed consent.

ABGC Certification Examination for Genetic Counselors

The ABGC Certification Examination assesses the knowledge, skills, and abilities required for competent practice as a genetic counselor.

200

Questions

240 min

Time Limit

70%

To Pass

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These practice questions were written with AI tools. They are not real exam questions. Exam facts are checked against the official sources listed below. Not reviewed by a subject-matter expert. Editorial policy

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