NM_000059.4:c.10027G>T (p.Glu3343Ter) is a nonsense variant in BRCA2 exon 27 that introduces a premature termination codon at position 3343 of 3418 amino acids. PVS1 is not applicable per ENIGMA BRCA2 Table 4: nonsense variants in exon 27 beyond codon p.E3309 are assigned PVS1_N/A, as truncation of the extreme C-terminus is not considered sufficient evidence for pathogenicity under the ENIGMA decision framework.¹ PM2_Supporting is met: the variant is absent from gnomAD v2.1 (non-cancer, exome), gnomAD v4.1 (non-cancer), and gnomAD-Canada v1.0 outbred populations.² PP3 is not met: although BayesDel no-AF score is 0.65 (≥0.30), the variant lies at position 3343, outside the BRCA2 clinically important functional domains (DNA binding domain aa 2481-3186; PALB2 binding domain aa 10-40). SpliceAI max delta is 0.17 (<0.20 threshold).³ BA1 and BS1 are not met: the variant is absent from gnomAD; filter allele frequency does not exceed benign population thresholds.⁴ PS3 and BS3 are not assessed: no variant-specific functional assay data were identified in ENIGMA Table 9 or in any of the six reviewed publications.⁵ PP4 and BP5 are not assessed: the variant was not present in the Li et al. 2020 (PMID:31853058) BRCA2 clinical-history likelihood-ratio table; no multifactorial likelihood data are available.⁶ ClinVar reports this variant as Likely benign (1 clinical laboratory, criteria provided, single submitter; variation ID 1770751). PP5 is not applicable under ENIGMA specifications, and no expert panel classification exists to warrant an override.⁷ With only PM2_Supporting met and PVS1 not applicable per ENIGMA Table 4, the available evidence is insufficient to classify this variant as pathogenic or likely pathogenic. Multiple evidence categories (functional, segregation, clinical history, case-control) lack data. The variant remains a variant of uncertain significance (VUS).