The c.566A>G variant in BRCA2 is a missense variant predicted to cause substitution of aspartic acid by glycine at amino acid 189 (p.(Asp189Gly)). This variant is absent from gnomAD v4.1 (read depth ≥25x in >90% samples, PM2_Supporting met). This BRCA2 missense variant has a SpliceAI score of 0.7, predicting an impact on splicing (score threshold ≥0.2) (PP3 not applied because a PVS1 code is met). This variant is reported to result in aberrant mRNA splicing. Minigene, RT-PCR, and RNAseq demonstrated that the variant causes deletion of part of the exon (r.562_631del), resulting in an out-of-frame transcript. The percent aberrant transcript produced from the variant allele using allele specific assessment with sequence analysis was determined to be >90% (ENIGMA unpublished data, Ambry internal data, Internal lab contributor). Final code strength determined by the rubric: PVS1 (RNA). 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, PVS1 (RNA)).