Germline BRCA2 variant with low variant allele frequency detected in tumor-only comprehensive genomic profiling

Germline BRCA1/2 variants in comprehensive genomic profiling (CGP) often exhibit variant allele frequency (VAF) exceeding 50%. However, when genomic loss occurs at the ipsilateral allele, including the germline variant in tumor cells, the VAF is low. This case report presents a patient with uterine sarcoma with a pathogenic BRCA2 mutation and low VAF in tumor-only CGP, which was later identified as a germline variant. When genomic alterations in BRCA1/2 are identified in tumor-only CGP, the possible germline origin of the variants should be considered, even if their VAF is very low.