The c.8378G>T variant in BRCA2 is a missense variant predicted to cause substitution of Glycine by Valine at amino acid 2793 (p.(Gly2793Val)). 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 a SpliceAI score of 0.36 predicts an impact on splicing (score threshold >0.20). The computational predictor BayesDel (noAF) gives a score of 0.59, above the recommended threshold of 0.3 for prediction of impact on BRCA2 function via protein change (PP3 met). Missense variant predicted to alter splicing, functional data considered only from assays that measure effect via mRNA and protein. Reported by two calibrated studies incorporating mRNA splicing effect to exhibit function similar to pathogenic control variants (PMIDs: 39779857, 39779848). Additionally, this variant is reported to exhibit function similar to pathogenic control variants in two assays with cDNA based design (PMIDs: 38417439, 32444794) (PS3 met). This variant is reported to result in aberrant mRNA splicing. RT-PCR and agarose gel electrophoresis demonstrated that the variant impacts splicing by exon 19 skipping (PMID: 32123317). The percent full-length and aberrant transcripts produced from the variant allele was not stated (PVS1 (RNA) and BP7_Strong (RNA) not met). Multifactorial likelihood ratio analysis using clinically calibrated data produced a combined LR for this variant of 0.87 (based on Family History LR=0.87), which is above the ENIGMA BRCA1/2 VCEP threshold for BP5 (>0.48) and below PP4 (<2.08) (BP5 and PP4 not met; PMID: 31853058). In summary, this variant meets the criteria to be classified as a Likely 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).