ABGC Certification Examination for Genetic Counselors — Questions and Answers

Question 1: Which organelle contains its own DNA?

Mitochondrion (Correct answer)
Endoplasmic reticulum
Ribosome
Nucleus

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

10–13 weeks (Correct answer)
22–24 weeks
After 28 weeks
15–20 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 3: Which role does a genetic counselor play in test interpretation?

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

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 4: 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 about termination options
Only information supporting continuation of the pregnancy
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 5: Which pedigree symbol represents a female in genetic counseling?

Triangle
Square
Circle (Correct answer)
Diamond

Correct answer: Circle

In pedigrees, circles are used to represent females.

Question 6: Which communication technique is most effective when disclosing a pathogenic variant result to a patient?

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

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

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

Correct answer: Its significance is not currently known

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

Question 8: Which informed consent element is MOST critical when discussing predictive genetic testing for a late-onset condition?

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

Question 9: The Bethesda guidelines for colorectal cancer testing were designed to identify tumors likely to show:

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

Correct answer: Microsatellite instability (MSI)

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

Question 10: Which result indicates a disease-causing mutation?

Pathogenic (Correct answer)
VUS
Benign
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 11: What is the term for a person who carries a gene for a genetic disorder but shows no symptoms?

Carrier (Correct answer)
Affected individual
Homozygote
Proband

Correct answer: Carrier

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

Question 12: 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
Ask the referring physician to reinforce the information
Use teach-back to reassess and re-explain with different framing (Correct answer)
Provide a pamphlet and schedule a follow-up

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 13: Why is nondirectiveness important in genetic counseling?

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

Correct answer: It promotes patient autonomy.

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

Question 14: In clinical sequencing, 'analytical validity' refers to:

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

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 15: 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 16: 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 17: What does autosomal recessive inheritance mean?

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

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

WGS generates a large number of variants of uncertain significance and incidental findings requiring interpretation (Correct answer)
WGS has lower sensitivity for detecting SNVs
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 19: The ACMG guideline criterion BS1 (allele frequency is greater than expected for disorder) is used as:

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

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

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

Correct answer: Trisomy 21 (Down syndrome)

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

Question 21: What is the human genome?

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

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

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

Correct answer: Motivational interviewing

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

Question 23: Peutz-Jeghers syndrome is characterized by hamartomatous polyps and mucocutaneous pigmentation and is caused by variants in:

PTEN
SMAD4
STK11 (LKB1) (Correct answer)
BMPR1A

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

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

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

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

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

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

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 27: The protein product of a dominant negative mutation typically:

Is completely absent, causing haploinsufficiency
Interferes with the function of the normal protein produced by the wild-type allele (Correct answer)
Gains a completely new function unrelated to the wild-type protein
Is expressed at twice the normal level due to gene duplication

Correct answer: Interferes with the function of the normal protein produced by the wild-type allele

Dominant negative mutations produce an abnormal protein that interferes with the normal protein (often in multimeric complexes), causing greater functional loss than simple haploinsufficiency would predict.

Question 28: The quad screen (maternal serum analytes) is a second-trimester screening test that includes which analytes?

AFP, hCG, PAPP-A, and NT
AFP, unconjugated estriol, PAPP-A, and inhibin A
AFP, hCG, unconjugated estriol, and inhibin A (Correct answer)
AFP, hCG, 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 29: The procedure-related pregnancy loss risk associated with amniocentesis is approximately:

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

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

Cumulative incidence
Attributable risk
Incidence
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 31: What is the main purpose of genomic testing?

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

Correct answer: To identify disease-related genetic variants

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

Question 32: 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?

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

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

ADA
FERPA
HIPAA
GINA (Correct answer)

Correct answer: GINA

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

Question 34: Which hereditary syndrome is associated with pathogenic variants in the BRCA1 and BRCA2 genes?

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

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 35: Why is psychological support essential in genetic counseling?

To ensure emotional well-being and informed decisions (Correct answer)
To assist with pharmacy orders
To conduct lab tests
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 36: Which of the following best describes a de novo mutation?

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

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

The square root of the population prevalence (Correct answer)
100% for identical twins
50% regardless of prevalence
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 38: Pharmacogenomics in clinical genetics focuses on:

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

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

A chromosomal translocation has occurred
A segment of DNA has been duplicated or deleted relative to the reference genome (Correct answer)
A single nucleotide has been changed
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 40: Which term describes sharing a patient's genetic information without consent?

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

Correct answer: Breach of confidentiality

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

Question 41: 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 42: Locus heterogeneity refers to the situation where:

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

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

Whether the condition is dominant or recessive
The number of genes involved in disease causation
The proportion of phenotypic variance in a population attributable to genetic factors (Correct answer)
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 44: When a genetic test result is reported as 'negative,' a genetic counselor should clarify that this means:

No pathogenic variant was identified in the genes tested, but residual risk may remain (Correct answer)
The patient is definitively unaffected and at population risk
The patient cannot be a carrier for the tested condition
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 45: What is consanguinity in genetic counseling?

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

Correct answer: Biological relationship between partners

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

Question 46: X-inactivation (lyonization) in females results in which of the following outcomes relevant to X-linked carrier females?

Preferential inactivation of the paternally derived X chromosome in all somatic cells
Complete inactivation of both X chromosomes leaving no X gene expression
Random inactivation of one X per cell that becomes fixed clonally, potentially leading to skewed X-inactivation in some tissues (Correct answer)
Equal expression of both X chromosomes in all cells throughout life

Correct answer: Random inactivation of one X per cell that becomes fixed clonally, potentially leading to skewed X-inactivation in some tissues

X-inactivation is random per cell but fixed clonally; extreme skewing toward inactivating the normal X can cause manifesting carrier females to express X-linked recessive conditions.

Question 47: 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)
Bladder cancer only
Testicular cancer only
No male-specific cancers

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

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

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 49: What does autosomal dominant inheritance imply?

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

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 50: Germline mosaicism occurs when a mutation is present in some but not all of a parent's germline cells. What is the primary clinical implication for genetic counseling?

The recurrence risk for future pregnancies is higher than the population risk but lower than 50%, making standard dominant inheritance risk estimates inaccurate (Correct answer)
Germline mosaicism only occurs for autosomal recessive conditions
The mutation cannot be detected in the parent by standard blood-based genetic testing, so recurrence risk is always 0%
The parent will show clinical features of the condition proportional to the level of mosaicism

Correct answer: The recurrence risk for future pregnancies is higher than the population risk but lower than 50%, making standard dominant inheritance risk estimates inaccurate

Germline mosaicism can produce multiple affected children from apparently unaffected parents; recurrence risk is greater than de novo rates but typically less than 50%, complicating risk counseling.

Question 51: What is the function of a gene?

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

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 52: 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
Three: pathogenic, benign, unknown
Two: pathogenic and benign only

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

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

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 54: Uniparental disomy (UPD) occurs when:

Two chromosomes exchange segments during recombination
Both copies of a chromosome pair are inherited from the same parent (Correct answer)
A segment of a chromosome is deleted and replaced by the other parental copy
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 55: How many pairs of chromosomes are typically found in human cells?

46
22
23 (Correct answer)
20

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

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

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

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

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

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

Correct answer: DNA methylation

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

Question 59: 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 1,000
1 in 50
1 in 2,000
1 in 385 (Correct answer)

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 60: What is the first step in genetic risk assessment?

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

Correct answer: Collect detailed family history.

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

Question 61: When counseling a couple for whom one partner is a carrier of an X-linked recessive condition, which reproductive outcome is CORRECT?

50% of sons will be affected and 50% of daughters will be carriers (Correct answer)
25% of all children will be affected
All sons will be affected
All daughters 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 62: Which of the following best describes 'variant of uncertain significance' (VUS) in the context of cancer genetics?

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

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

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

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

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

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

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

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 66: Uniparental disomy (UPD) can cause disease even in the absence of a traditional mutation. Which mechanism most commonly explains pathogenicity of UPD?

Disruption of imprinted gene dosage when both copies derive from one parent (Correct answer)
Both copies of a chromosome carry a heterozygous mutation
Replication error causing copy number variation
Mitotic recombination producing loss of heterozygosity

Correct answer: Disruption of imprinted gene dosage when both copies derive from one parent

UPD causes disease primarily by disrupting imprinted loci—when both copies come from one parent, imprinted genes that should be expressed from only the maternal or paternal allele are either doubly silenced or doubly expressed.

Question 67: 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 68: What is a potential psychosocial response to genetic testing results?

Anxiety (Correct answer)
Increased sleep duration
Euphoria
Increased appetite

Correct answer: Anxiety

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

Question 69: Lynch syndrome is caused by pathogenic variants in which set of genes?

APC, MUTYH, NTHL1
BRCA1, BRCA2, PALB2
MLH1, MSH2, MSH6, PMS2, EPCAM (Correct answer)
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 70: Which type of mutation involves the insertion of one or two nucleotides, causing a shift in the reading frame of downstream codons?

Silent mutation
Missense mutation
Frameshift mutation (Correct answer)
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 71: In the context of genetic counseling, 'nondirectiveness' primarily means the counselor should:

Refuse to give any recommendations
Always present options neutrally without any guidance
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 72: Which term describes the increased frequency of a condition in offspring of consanguineous couples compared with the general population?

Heterozygote advantage
Autozygosity (Correct answer)
Pleiotropy
Penetrance

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

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

Correct answer: Cultural beliefs

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

Question 74: 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?

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

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

All patients with breast cancer
Patients over age 70 with any cancer
All patients diagnosed with colorectal cancer (Correct answer)
Patients with no family history of 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 76: Whole exome sequencing (WES) sequences:

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

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 77: Why is the proband important in risk assessment?

They are the oldest family member.
They initiate the family health analysis. (Correct answer)
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 78: What is a limitation of direct-to-consumer genetic tests?

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

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 79: The phenomenon of 'anticipation' in cancer genetics refers to:

Earlier age of cancer onset in a patient who is anxious about their diagnosis
Physicians anticipating a positive genetic test result before testing
The expectation that all carriers will develop cancer
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 80: What does exome sequencing analyze?

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

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 81: Which type of test examines many genes at once?

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

Correct answer: Panel testing

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

Question 82: Which condition is commonly inherited in an autosomal dominant pattern?

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

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

0.18 (18%) (Correct answer)
0.02 (2%)
0.81 (81%)
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 84: 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)
Percentages only (e.g., 25%)
Odds ratios (e.g., 3:1)
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 85: Genetic counselors use Bayesian analysis in clinical genetics primarily to:

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)
Estimate the population frequency of a variant
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 86: Multiple endocrine neoplasia type 2 (MEN2) is caused by germline pathogenic variants in which gene?

VHL
NF1
RET (Correct answer)
SDHA

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

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

Correct answer: Lynch syndrome

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

Question 88: What is the role of chromosomes in genetics?

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

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 89: Which ethical principle emphasizes doing good for the patient?

Justice
Nonmaleficence
Beneficence (Correct answer)
Autonomy

Correct answer: Beneficence

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

Question 90: Which evidence criterion is classified as 'very strong pathogenic' (PVS1) in ACMG/AMP variant interpretation?

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

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 91: 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
Whole-body MRI annually, with brain MRI and breast MRI included (Correct answer)
Annual mammography starting at age 40 only
No surveillance needed until symptoms arise

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 92: 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:

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

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 93: Which of the following best describes the concept of incomplete penetrance versus variable expressivity?

Incomplete penetrance applies only to recessive conditions; variable expressivity applies only to dominant conditions
Both terms are interchangeable and describe the same phenomenon
Incomplete penetrance refers to whether the genotype produces any phenotype at all; variable expressivity refers to the range of phenotypic severity among those who are affected (Correct answer)
Incomplete penetrance means the trait skips generations; variable expressivity means the trait is always mild

Correct answer: Incomplete penetrance refers to whether the genotype produces any phenotype at all; variable expressivity refers to the range of phenotypic severity among those who are affected

Penetrance is the proportion of individuals with a pathogenic genotype who show any phenotypic manifestation; expressivity describes the spectrum of severity or features among those who do manifest the condition.

Question 94: Which condition is typically associated with autosomal recessive inheritance?

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

Correct answer: Cystic fibrosis

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

Question 95: 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 50 (Correct answer)
1 in 100
1 in 10,000
1 in 200

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 96: 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 97: Confined placental mosaicism (CPM) is a limitation unique to which prenatal diagnostic procedure?

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

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

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

Correct answer: Mismatch repair

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

Question 99: The founder effect in genetics refers to:

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

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

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

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 101: 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
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)
Hamartomatous polyps throughout the GI tract

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 102: Which of the following describes 'pleiotropy'?

One gene locus affected by multiple different variants
A gene expressed differently in males versus females
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 103: Variable expressivity in genetics means:

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)
Some pathogenic variants are more severe than others in the same individual
The gene is only expressed in males

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 104: Which inheritance pattern is characterized by mitochondrial DNA mutations transmitting exclusively through the maternal line with all offspring of an affected mother being at risk?

Autosomal dominant inheritance
Mitochondrial (maternal) inheritance (Correct answer)
X-linked dominant inheritance
Autosomal recessive inheritance

Correct answer: Mitochondrial (maternal) inheritance

Mitochondrial DNA is maternally inherited because virtually all mitochondria in the zygote derive from the egg; therefore, an affected mother transmits the mutation to all her children, but an affected father does not transmit it.

Question 105: Which term describes the situation where a single gene mutation causes multiple, seemingly unrelated phenotypic effects?

Epistasis
Genetic heterogeneity
Pleiotropy (Correct answer)
Variable expressivity

Correct answer: Pleiotropy

Pleiotropy refers to the phenomenon where a single gene mutation produces effects in multiple organ systems or tissues, as seen in Marfan syndrome (cardiac, skeletal, and ocular features from FBN1 mutations).

Question 106: Genetic drift is MOST significant in:

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

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

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
Encourage the patient to reconsider by emphasizing the benefits

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

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

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

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

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 110: The term 'diagnostic yield' in clinical genetics refers to:

The proportion of tested individuals who receive a molecular diagnosis from a given test (Correct answer)
The cost efficiency of a genetic test
The number of variants reported per patient
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 111: A copy number variant (CNV) is best defined as:

An epigenetic modification that alters gene expression without changing sequence
A trinucleotide repeat expansion beyond the normal range
A single nucleotide change that alters a codon's amino acid
A structural variation involving a segment of DNA ≥1 kb that differs in copy number between individuals (Correct answer)

Correct answer: A structural variation involving a segment of DNA ≥1 kb that differs in copy number between individuals

CNVs are structural genomic variants ≥1 kb involving deletions, duplications, or other rearrangements that result in variation in the number of copies of that segment compared to a reference genome.

Question 112: A patient with limited health literacy is seen for BRCA testing counseling. The BEST approach is to:

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

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 113: A splicing mutation that activates a cryptic splice site would most likely result in which of the following?

Complete absence of any mRNA transcript
A protein with a single amino acid substitution
Expansion of a trinucleotide repeat within the coding sequence
An mRNA with an additional segment of intronic sequence or deletion of exonic sequence (Correct answer)

Correct answer: An mRNA with an additional segment of intronic sequence or deletion of exonic sequence

Cryptic splice site activation causes the spliceosome to use an alternative splice site, incorporating intronic sequence into the mRNA or skipping part of an exon, altering the protein.

Question 114: Chromosomal microarray analysis (CMA) is MOST appropriate as a first-tier test for:

Individuals with intellectual disability, autism spectrum disorder, or multiple congenital anomalies (Correct answer)
Patients with suspected trinucleotide repeat disorders
Patients with a known familial pathogenic single-nucleotide variant
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 115: In the context of clinical molecular testing, 'sensitivity' is defined as:

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

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

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

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 117: 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 118: A point mutation at the first position of a codon changes AUG (methionine/start) to AUG → AUA. This change would most likely result in:

Loss of the start codon, preventing normal translation initiation from that site (Correct answer)
A frameshift disrupting all downstream codons
A conservative amino acid change with minimal functional effect
Nonsense-mediated mRNA decay

Correct answer: Loss of the start codon, preventing normal translation initiation from that site

Mutation of the initiator ATG codon eliminates the canonical translation start signal, preventing ribosomal assembly at that site and often abolishing or severely reducing protein production.

Question 119: 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
Contact family members directly on the patient's behalf
Provide the patient with tools and guidance to share the information themselves (Correct answer)

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

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

Correct answer: 25%

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

Question 121: A nuchal translucency (NT) measurement of ≥3.5 mm at 11–14 weeks is associated with increased risk for:

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

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 122: Locus heterogeneity in genetics means that:

The same disease phenotype can result from mutations at different genetic loci (Correct answer)
Two alleles at the same locus produce different disease severity
Different mutations at the same locus produce different diseases
A single genetic locus produces multiple different disease phenotypes

Correct answer: The same disease phenotype can result from mutations at different genetic loci

Locus heterogeneity occurs when the same clinical phenotype can be caused by mutations in different genes (e.g., retinitis pigmentosa is caused by mutations in over 60 different genes).

Question 123: A patient asks about the difference between a 'screen positive' and a 'diagnostic positive' result for Down syndrome. The counselor correctly explains that:

Screen positives are used only for research purposes
A diagnostic positive is less reliable than a screen positive
Both terms mean the same thing clinically
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 124: Loss of heterozygosity (LOH) in tumor cells most often represents which event according to Knudson's two-hit hypothesis?

Germline mutation in a DNA repair gene
Activation of an oncogene on the wild-type allele
Somatic inactivation of the remaining wild-type tumor suppressor allele (Correct answer)
Epigenetic silencing of an oncogene

Correct answer: Somatic inactivation of the remaining wild-type tumor suppressor allele

In hereditary cancer syndromes, the first hit is the inherited germline mutation; LOH in tumor tissue represents somatic inactivation (the second hit) of the remaining wild-type allele of the tumor suppressor gene.

Question 125: 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 126: Preimplantation genetic testing for aneuploidy (PGT-A) is used to:

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

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

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

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

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

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

Variable expressivity
Incomplete penetrance
Anticipation
Genomic imprinting (Correct answer)

Correct answer: Genomic imprinting

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

Question 130: A mosaic pathogenic variant found in an individual means:

The variant is present in a pseudogene
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

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 131: 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 have a higher reproductive rate by chance
The CF allele mutates frequently from normal alleles
CF carriers may have had increased resistance to certain infectious diseases such as cholera (Correct answer)

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

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

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 133: Which of the following describes a mutation?

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

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 134: Which technology is commonly used in genomic sequencing?

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

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 135: Why is family history still relevant with genomic testing?

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

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 136: 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 137: During meiosis I, homologous chromosomes exchange segments in a process called:

Independent assortment
Sister chromatid exchange
Crossing over (recombination) (Correct answer)
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 138: Penetrance in genetics refers to:

The proportion of individuals with a given genotype who exhibit the associated phenotype (Correct answer)
The severity of disease in affected individuals
The number of genes responsible for a condition
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 139: Which of the following correctly distinguishes an oncogene from a tumor suppressor gene regarding mechanism of cancer causation?

Oncogenes require loss of both alleles; tumor suppressors require gain of function in one allele
Oncogenes cause cancer by gain-of-function mutations acting dominantly; tumor suppressors cause cancer when both alleles are inactivated (recessive) (Correct answer)
Oncogenes are only activated by chromosomal translocations; tumor suppressors are only inactivated by point mutations
Oncogenes and tumor suppressors are functionally identical but differ in chromosomal location

Correct answer: Oncogenes cause cancer by gain-of-function mutations acting dominantly; tumor suppressors cause cancer when both alleles are inactivated (recessive)

Oncogenes act dominantly—a single gain-of-function mutation drives uncontrolled cell growth—whereas tumor suppressor genes act recessively, requiring biallelic inactivation to lose growth control.

Question 140: Genomic imprinting results in conditions where disease expression depends on:

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

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

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

Correct answer: To authorize genetic testing with full understanding

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

Question 142: Which of the following BEST describes the purpose of a pedigree in a genetic counseling session?

To satisfy documentation requirements only
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

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

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

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 144: Heteroplasmy in mitochondrial genetics refers to:

The presence of two alleles at a nuclear locus in a diploid cell
Recombination between paternal and maternal mitochondrial genomes
The exclusive presence of mutant mitochondrial DNA throughout all cells
A mixture of two or more mitochondrial DNA genotypes within a cell or individual (Correct answer)

Correct answer: A mixture of two or more mitochondrial DNA genotypes within a cell or individual

Heteroplasmy describes the coexistence of wild-type and mutant mitochondrial DNA within the same cell or tissue; the proportion of mutant mtDNA (mutation load) influences clinical severity.

Question 145: Preimplantation genetic testing for monogenic conditions (PGT-M) requires which INITIAL step?

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

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 146: 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 147: Which PTEN-related syndrome is associated with an increased risk of breast, thyroid, endometrial, and colorectal cancers along with macrocephaly?

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

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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Exam Rules

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Unanswered questions count as wrong — answer everything
10 pretest questions are mixed in and don't affect your score
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