The c.442-22_442-13del variant is an intronic variant occurring in intron 6 of the BRCA1 gene. This deletion variant was not observed in gnomAD v2.1 (exomes only, non-cancer subset) or gnomAD v3.1 (non-cancer subset), but PM2_Supporting was not applied since recall is suboptimal for this type of variant (PM2_Supporting not met). This variant is reported to result in aberrant mRNA splicing. RT-PCR and qPCR assays demonstrated that the variant impacts splicing by activation of a cryptic acceptor site, resulting in a 59nt intron retention of intron 6. Combination of non-allele specific assay results (PMIDs: 10323242, 32745242) and assessment of full-length transcript quantification by real-time PCR in carriers (personal communication) suggests a near complete splicing effect. Appropriate code strength determined by comparison of results to PVS1 decision tree and assessment of mRNA splicing data (PVS1_Strong (RNA) met). Cosegregation analysis of family(ies) carrying this variant provided evidence towards pathogenicity, and has a Bayes Score of 48.83, within the thresholds for strong pathogenic evidence (LR >18.7 & ≤350) (PP1_Strong met; PMID: 32745242, Internal lab contributors). Multifactorial likelihood ratio analysis using clinically calibrated data produced a combined LR for this variant of 4.83 (based on Pathology LR=4.83), within the thresholds for Moderate evidence towards pathogenicity (LR >4.3 & ≤18.7) (PP4_Moderate met; 32745242, Internal lab contributors). In summary, this variant meets the criteria to be classified as a Pathogenic variant for BRCA1-related cancer predisposition based on the ACMG/AMP criteria applied as specified by the ENIGMA BRCA1/2 VCEP (PVS1_Strong (RNA), PP1_Strong, PP4_Moderate).