Homologous recombination deficiency-driven genomic instability in ovarian cancer as an indicator of BRCA1 and BRCA2 variant pathogenicity

Genomic instability scores for HRD in high-grade ovarian cancer provide robust evidence for BRCA1 and BRCA2 variant classification according to ACMG/AMP criteria. Analysis of 4,943 tumors resulted in an evidence strengh of supporting pathogenic for HRD-GIShigh and moderate benign for HRD-GISlow, highlighting the clinical utility of genomic instability testing for refining BRCA1 and BRCA2 variant interpretation.