Laboratory Genetics & Variant Interpretation Flashcards

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:

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.

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

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.

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

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.

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

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.

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

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.

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

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.