Reclassification of VUS in <i>BRCA1</i> and <i>BRCA2</i> using the new <i>BRCA1</i>/<i>BRCA2</i> ENIGMA track set demonstrates the superiority of ClinGen ENIGMA Expert Panel specifications over the standard ACMG/AMP classification system.

ABSTRACT:

Purpose

Variants of uncertain significance (VUS) are considered one of the most significant impediments to the translation of genetic test results into precise clinical recommendations. The 2015 American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) classification guidelines established a general framework for the assessment and classification of genetic variants; yet, gene-specific specifications are needed to enable better variant classification to reduce the number of VUS. The process of gene-specific adaptations of the ACMG/AMP codes is led and accompanied by ClinGen and implemented by Variant Curation Expert Panels (VCEP). The Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) VCEP recently published its

SUBMITTER: Benet-Pages A 

PROVIDER: S-EPMC11869971 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature