The BRCA2 c.4516T>C (p.Phe1506Leu; p.F1506L) variant has been reported in ClinVar with conflicting classifications, including uncertain significance and likely benign submissions.
clinvar ↗This variant is absent from gnomAD v2.1 and present at very low frequency in gnomAD v4.1 (3/1,613,958 alleles; AF 0.00019%), with the highest observed frequency 1/6,062 alleles in the Middle Eastern population (AF 0.01650%).
gnomad_v2 ↗ gnomad_v4 ↗No variant-specific calibrated functional assay classification was identified in the reviewed BRCA2 ENIGMA functional tables, and no variant-specific reviewed functional evidence was identified in curated somatic reviewer resources.
oncokb ↗The substitution lies outside the BRCA2 clinically important domains defined by ENIGMA, SpliceAI predicts no significant splice effect (max delta score 0.00), and missense predictor scores are low (REVEL 0.093; BayesDel no-AF -0.650576), supporting a benign computational profile.
cspec ↗ spliceai ↗
