AimsClinical guidelines recommend testing both germline and tumour DNA for BRCA1/2pathogenic variants (PVs) in non-mucinous high-grade epithelial ovarian cancer (NMEOC). In this study, we show that some tumour BRCA1/2PVs are highly likely to be somatic based on certain clinical and variant characteristics, meaning it may not be necessary to test all NMEOC cases for germline BRCA1/2PVs.MethodsAn observational study that included all tumour BRCA1/2PVs detected in cases of NMEOC in the Northwest of England between July 2017 and February 2022. All tumour BRCA1/2PVs were compared with PVs recorded in a prospectively gathered pan-cancer germline BRCA1/2(gBRCA) testing database for the same geographical region (gBRCA1PVs=910 and gBRCA2PVs=922). Tumour BRCA1/2PVs were categorised as common (≥1%), uncommon (<1%) or absent from the germline database.ResultsOne hundred and thirteen tumour BRCA1/2PVs were detected in 111 NMEOC cases. There were 69 germline and 44 somatic variants. The mean age at diagnosis for gBRCAand somatic BRCA1/2(sBRCA) PVs was 56.9 and 68.5 years, respectively (Student's t-test p<0.0001). All sBRCAPVs were detected in non-familial cases. All tumour BRCA1/2PVs with a variant allele frequency (VAF) <35% in non-familial cases were somatic variants. Eighty-one per cent of germline-tumour BRCA1/2PVs were present (common=31, uncommon=25) in the gBRCAtesting database, while 89% of somatic-tumour BRCA1/2PVs were absent (n=39).ConclusionsWe predict the likelihood of a tumour BRCA1/2PV being somatic is 99.8% in non-familial cases of NMEOC diagnosed aged ≥75, where the VAF is ≤30% and there is no regional germline commonality.