The BRCA2 c.8242G>A (p.Gly2748Ser; G2748S) variant has been reported in ClinVar, where the current expert-panel overall classification is uncertain significance, while multiple clinical laboratory submissions classify it as likely pathogenic or pathogenic.
clinvar ↗This variant is present at very low frequency in population databases, including gnomAD v2.1 at 3/249070 alleles (AF 1.20e-05; grpmax FAF 9.58e-06) and gnomAD v4.1 at 6/1614064 alleles (AF 3.72e-06), which is below ENIGMA BS1 and BA1 thresholds but means PM2 is not met because the variant is not absent from controls.
gnomad_v2 ↗ gnomad_v4 ↗ cspec ↗In the ENIGMA BRCA2 functional evidence table, this exact variant is assigned PS3 at strong strength based on one calibrated study reported to show a damaging functional effect consistent with pathogenic control variants.
This missense change lies within the BRCA2 DNA-binding domain; BayesDel no-AF is 0.454479, above the ENIGMA PP3 threshold of 0.30, SpliceAI predicts no significant splice effect with a maximum delta score of 0.06, and REVEL is 0.842, supporting a damaging protein effect without predicted splice disruption.
cspec ↗ spliceai ↗
