Identification of a Pathogenic BRCA2 Variant by Multigene Panel Testing in a Blood Group Chimera/Mosaic Case Unclassifiable by Conventional BRCA1/2 Testing

In the setting of blood group chimerism/mosaicism, conventional BRCA1/2 genetic testing may yield inconclusive results. Multigene panel testing (MGPT) may overcome this limitation. We report a case in which BRCA2 pathogenic variant status was successfully determined using MGPT after standard testing was deemed uninterpretable. A 48-year-old woman with locally advanced bilateral breast cancer had a maternal history of breast cancer associated with a pathogenic BRCA2 variant. The patient expressed a clear intention to undergo risk-reducing salpingo-oophorectomy (RRSO) if she were confirmed to carry the same pathogenic variant. Single-site BRCA2 testing was initially performed but resulted in an indeterminate outcome due to blood group chimerism/mosaicism. Subsequently, MGPT was conducted and successfully identified the same pathogenic BRCA2 variant as detected in her mother, providing clinically actionable information that directly informed the patient’s preventive decision-making. RRSO was performed, and no malignant findings were identified in the resected adnexal tissues. Thus, when blood group chimerism/mosaicism produces discordant genetic profiles and renders single-gene testing inconclusive, MGPT may provide a definitive hereditary cancer diagnosis and guide appropriate risk-reduction strategies.