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

Three: pathogenic, benign, unknown

Answer

Four: pathogenic, likely pathogenic, benign, likely benign

Answer

Two: pathogenic and benign only

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

The variant is observed in multiple unrelated affected individuals

Answer

The variant is absent from population databases

Answer

Functional studies demonstrate a damaging effect

Question 3

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

Accepted Answer

Targeted sequencing of selected disease-relevant genes

Answer

Sequencing the entire genome at high depth

Answer

Single-gene Sanger sequencing

Answer

Cytogenetic karyotyping

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

Patients with a known familial pathogenic single-nucleotide variant

Answer

Carrier screening in couples planning pregnancy

Answer

Patients with suspected trinucleotide repeat disorders

Question 5

Whole exome sequencing (WES) sequences:

Accepted Answer

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

Answer

The entire genome including intergenic regions

Answer

Only known disease-causing genes

Answer

Mitochondrial DNA exclusively

Question 6

A mosaic pathogenic variant found in an individual means:

Accepted Answer

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

Answer

Two different pathogenic variants are present in the same gene

Answer

The variant was inherited from both parents

Answer

The variant is present in a pseudogene