In ACMG variant classification, what does the term 'Variant of Unknown Significance' (VUS) stand for?

In ACMG variant classification, what does the term 'Variant of Unknown Significance' (VUS) stand for?

• A. Benign
• B. Likely Benign
• C. Pathogenic
• D. Variant of Unknown Significance

Answer: (D)

In ACMG variant classification, a Variant of Unknown Significance is a variant for which there isn’t enough evidence to determine whether it is benign or disease-causing. It signals uncertainty: the data available so far don’t tip the balance toward a benign interpretation or toward pathogenicity. Because of that, a VUS should not be used to guide clinical decisions, and it may be reclassified later as more information becomes available (e.g., population data, functional studies, or family segregation). The other terms describe variants with clearer implications: benign or likely benign are not associated with disease, while pathogenic or likely pathogenic are considered disease-ca-causing.

In ACMG variant classification, a Variant of Unknown Significance is a variant for which there isn’t enough evidence to determine whether it is benign or disease-causing. It signals uncertainty: the data available so far don’t tip the balance toward a benign interpretation or toward pathogenicity. Because of that, a VUS should not be used to guide clinical decisions, and it may be reclassified later as more information becomes available (e.g., population data, functional studies, or family segregation). The other terms describe variants with clearer implications: benign or likely benign are not associated with disease, while pathogenic or likely pathogenic are considered disease-ca-causing.