NM_007294.4:c.2657_2676del is a 20bp frameshift deletion in BRCA1 exon 10(11) that creates a premature termination codon at p.Ser886Ter. BRCA1 loss of function is an established mechanism for hereditary breast and ovarian cancer.¹ Per ENIGMA BRCA1 VCEP Specifications Table 4, PTC variants in exon E10(11) are assigned PVS1 (Very Strong) as null variants in a gene where loss of function is a known disease mechanism, and PM5_Strong (PTC) because other proven pathogenic PTC variants have been reported in this exon.² The variant is absent from gnomAD v2.1 and v4.1 population databases (allele count = 0), meeting PM2 at Supporting strength per ENIGMA population frequency rules.³ Applying the ENIGMA Table 3 point system: PVS1 Very Strong = 8 points, PM5 Strong = 4 points, PM2 Supporting = 1 point. Total = 13 points, which falls in the Pathogenic range (>=10).⁴