A Family With Discordant Germline BRCA1 and BRCA2 Variants: A BRCA1-Positive Mother and BRCA2-Positive Daughter With Possible Paternal Inheritance.

Hereditary breast and ovarian cancer (HBOC) is primarily caused by germline pathogenic variants in BRCA1 or BRCA2. Although a single pathogenic variant usually explains cancer predisposition within a family, independent pathogenic variants may coexist and complicate risk assessment and genetic counseling. We report a 43-year-old woman with right breast cancer in whom germline genetic testing identified a pathogenic BRCA2 variant, c.2808_2811del (p.Ala938ProfsTer21). Her mother developed primary peritoneal carcinoma at the age of 77. Tumor genomic testing identified a BRCA1 deletion of exons 1-12, which was subsequently confirmed as a germline variant. No pathogenic BRCA2 variant was detected in the mother. These discordant findings suggest that the daughter's BRCA2 variant may have been inherited through the paternal lineage or may have arisen de novo. The father was deceased and unavailable for genetic testing, and the paternal family history was uninformative. This case demonstrates that multiple independent BRCA pathogenic variants may coexist within a single family. Restricting cascade testing to a single known familial variant may therefore result in incomplete hereditary cancer risk assessment. Comprehensive germline evaluation and individualized, pedigree-based genetic counseling should be considered when clinical findings are discordant with a known familial variant.