BRCA2 encodes a DNA repair protein that maintains genome stability by repairing double-strand breaks through homologous recombination and by protecting DNA replication forks. It acts as a tumor suppressor, and inherited loss-of-function changes cause hereditary breast and ovarian cancer syndrome, with elevated lifetime risks of breast, ovarian, prostate, and pancreatic cancers; biallelic changes cause Fanconi anemia complementation group D1. Reduced or altered BRCA2 activity is implicated in multiple tumor types, and PARP inhibitors are an approved treatment for BRCA2-associated ovarian and breast cancers.
BRCA2 loss-of-function variants cause hereditary breast and ovarian cancer syndrome, yet this variant is a missense change (p.Thr3371Ala) of uncertain significance: available evidence neither establishes nor rules out pathogenicity. Clinically, it means the variant cannot yet be used to confirm or exclude BRCA2-related cancer risk, and its classification may change as more evidence accumulates.
No ENIGMA BRCA1/2 v1.2 criteria-combination rule was satisfied because no criterion was met, and the zero evidence point score falls in the -1 to 5 VUS band, yielding a final classification of Variant of Uncertain Significance.
No criteria were applied for this variant.
East Asian 9 / 44,898 |
0.02% |
Remaining individuals 8 / 62,486 |
0.013% |
East Asian 2 / 19,952 |
0.01% |
East Asian 6 / 1,338 |
0.45% |
Remaining individuals 2 / 1,138 |
0.18% |
