The c.7787G>T variant in BRCA2 is a missense variant predicted to cause substitution of Glycine by Valine at amino acid 2596 (p.(Gly2596Val)). This variant is absent from gnomAD v4.1 (read depth ≥25x in >90% samples, PM2_Supporting met). This BRCA2 missense variant is within a key functional domain and the computational predictor BayesDel (noAF) gives a score of 0.45, above the recommended threshold of 0.30 for prediction of impact on BRCA2 function via protein change. A SpliceAI score of 0.15 indicates an unclear predicted impact on splicing (score threshold 0.10-0.20) (PP3 met). Reported by three calibrated studies to exhibit protein function similar to pathogenic control variants (PMIDs: 38417439, 39779857, 39779848) (PS3 met). Multifactorial likelihood ratio analysis using clinically calibrated data produced a combined LR for this variant of 2273.3 (based on Cosegregation LR=1733.4; Pathology LR=4.86; Family History LR=0.27), above the thresholds for very strong evidence towards pathogenicity (LR >350) (PP4_Very strong met; PMID: 34597585, 31131967, Internal lab contributor). In summary, this variant meets the criteria to be classified as a Pathogenic variant for BRCA2-related cancer predisposition based on the ACMG/AMP criteria applied as specified by the ENIGMA BRCA1/2 VCEP (PM2_Supporting, PP3, PS3, PP4_Very strong).