The c.67G>A variant in BRCA2 is a missense variant predicted to cause substitution of Aspartic Acid by Asparagine at amino acid 23 (p.(Asp23Asn)). This variant is absent from gnomAD v2.1 (exomes only, non-cancer subset, read depth ≥25) and gnomAD v3.1 (non-cancer subset, read depth ≥25) (PM2_Supporting met). This BRCA2 missense variant has a SpliceAI score of 0.59, predicting an impact on splicing (score threshold >0.20) (PP3 not applied because a PVS1 code is met). This variant is reported to result in aberrant mRNA splicing. RT-PCR demonstrated that the variant impacts splicing by use of a cryptic site 4 nt upstream (PMID: 29750258). The percent reference and aberrant transcripts produced from the variant allele is not stated. A minigene assay demonstrated the variant allele produced 7.7 % reference (full-length, FL) and 89 % aberrant transcript using an allele specific quantitative assessment with Capillary electrophoresis (PMID: 30883759). RT-PCRseq from an Internal lab contributor has also demonstrated that a small number of normally spliced reads contained the variant allele (Ambry internal data). Appropriate code strength determined by comparison of results to PVS1 decision tree and VCEP discussion: PVS1_Strong (RNA). In summary, this variant meets the criteria to be classified as a Variant of uncertain significance for BRCA2-related cancer predisposition based on the ACMG/AMP criteria applied as specified by the ENIGMA BRCA1/2 VCEP (PM2_Supporting, PVS1_Strong (RNA)).