NM_007294.4:c.2182A>T (p.Arg728Ter) is a nonsense variant in BRCA1 exon 10 (legacy exon 11), predicted to undergo nonsense-mediated decay (>1900 nt upstream of the terminal exon junction).¹ Per ENIGMA Specification Table 4, BRCA1 exon 10 PTC variants are assigned PVS1 (Very Strong) weight. Loss of function is an established disease mechanism for BRCA1.² ENIGMA Specification Table 4 assigns PM5_Strong (PTC) for nonsense variants in BRCA1 exon 10, where multiple proven pathogenic PTC variants have been observed. This is supported by ≥4 evidence points across functional assay, case-control, personal/family history, and CIMBA data (Supplementary Table 1).³ The variant is absent from gnomAD v2.1 (non-cancer, exome only), gnomAD v4.1 (non-cancer), and gnomAD-Canada v1.0, meeting ENIGMA PM2_Supporting.⁴ ENIGMA point-based combining rules (Table 3): PVS1 Very Strong (8 points) + PM5 Strong (4 points) + PM2 Supporting (1 point) = 13 points, meeting the Pathogenic threshold (≥10 points).⁵