FIGURE 2: Incorporation of HDR functional data into a clinical ACMG/AMP framework for variant classification.

BRCA2 DBD missense variants observed clinically by GeneDx were classified by an ACMG/AMP-like framework into five categories: PATH (pathogenic), LPATH (likely pathogenic), VUS (variants of uncertain significance), LBEN (likely benign), BEN (benign). The PATH and LPATH categories were combined, LBEN and BEN categories were combined. The number of variants in each classification category defined by ClinVar (ClinGen approved laboratories excluding GeneDx) and by GeneDx before and after applying HDR functional data are shown.