BackgroundThe distribution of ovarian tumour characteristics differs between germlineBRCA1andBRCA2pathogenic variant carriers and non-carriers. In this study, we assessed the utility of ovarian tumour characteristics as predictors ofBRCA1andBRCA2variant pathogenicity, for application using the American College of Medical Genetics and the Association for Molecular Pathology (ACMG/AMP) variant classification system.MethodsData for 10,373 ovarian cancer cases, including carriers and non-carriers ofBRCA1orBRCA2pathogenic variants, were collected from unpublished international cohorts and consortia and published studies. Likelihood ratios (LR) were calculated for the association of ovarian cancer histology and other characteristics, withBRCA1andBRCA2variant pathogenicity. Estimates were aligned to ACMG/AMP code strengths (supporting, moderate, strong).ResultsNo histological subtype provided informative ACMG/AMP evidence in favour ofBRCA1andBRCA2variant pathogenicity. Evidence against variant pathogenicity was estimated for the mucinous and clear cell histologies (supporting) and borderline cases (moderate). Refined associations are provided according to tumour grade, invasion and age at diagnosis.ConclusionsWe provide detailed estimates for predictingBRCA1andBRCA2variant pathogenicity based on ovarian tumour characteristics. This evidence can be combined with other variant information under the ACMG/AMP classification system, to improve classification and carrier clinical management.