The variant is BRCA2 NM_000059.4:c.341A>G, p.(His114Arg), a missense substitution at residue 114.
Under the BRCA2 ENIGMA specification, BP1_Strong applies to missense variants outside clinically important functional domains with no predicted splice impact. Residue 114 is outside the BRCA2 domains used by this framework (aa 10-40 and aa 2481-3186), and SpliceAI predicts no significant splice effect (max delta 0.03).
cspec ↗Population data support BS1_Supporting because gnomAD v2.1 grpmax FAF is 7.443e-05, which falls within the BRCA2 BS1_Supporting range (>0.00002 and ≤0.0001).
gnomad_v2 ↗The ENIGMA multifactorial dataset does not support pathogenic enrichment: for c.341A>G the combined LR is 0.5897487000827281 and the sheet comments that the combined LR is not <0.5 or >2, so PS4/BS4-type multifactor evidence is not met.
No calibrated damaging or benign functional assay assignment for this variant was identified in the curated ENIGMA functional table, so PS3 and BS3 were not applied.
Overall, the assembled workspace supports a benign-leaning VCEP classification without conflicting pathogenic evidence sufficient to retain VUS; the best fit is Likely benign.
