CGC Laboratory Genetics & Variant Interpretation

Question 1

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

Accepted Answer

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

Answer

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

Question 2

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

Accepted Answer

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

Answer

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

Question 3

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

Accepted Answer

Targeted sequencing of selected disease-relevant genes

Answer

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

Question 4

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

Accepted Answer

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

Answer

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 5

Whole exome sequencing (WES) sequences:

Accepted Answer

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

Answer

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.

CGC - Certified Genetic Counselor Practice Test

CGC - Certified Genetic Counselor Practice Test

CGC Laboratory Genetics & Variant Interpretation