NM_000059.4:c.7977-15T>G is an intronic substitution located 15 bases upstream of BRCA2 exon 18, outside the canonical acceptor splice site consensus (+/-1,2). SpliceAI predicts no significant impact on splicing (max delta = 0.03), supporting a benign bioinformatic assessment under ENIGMA BP4_Supporting.¹ This variant is extremely rare in population databases, present in 2 of 1,604,172 alleles in gnomAD v4.1 (AF = 1.25e-06), both in the European non-Finnish population. It is absent from gnomAD v2.1. The FAF of 2.8e-07 does not meet ENIGMA BS1 thresholds for benign population evidence, nor does it meet BA1 stand-alone benign criteria.² In a multifactorial likelihood analysis by Parsons et al. 2019 (PMID:31131967), this variant had a combined likelihood ratio of 1.11 (co-occurrence LR = 1.02; family history LR = 1.08), which falls within the neutral zone and does not provide evidence for either pathogenicity (PP4) or benignity (BP5).³ The variant has been reported in ClinVar as Likely benign by 4 clinical laboratories and as Uncertain significance by 2 laboratories (ClinVar ID: 96863), though no expert panel classification has been assigned.⁴ The adjacent canonical splice acceptor variant c.7977-1G>C is a well-established pathogenic variant (Parsons et al. 2019 posterior probability = 0.999; IARC Class 5), but c.7977-15T>G does not disrupt the splice consensus and is predicted to be splicing-neutral by SpliceAI.⁵ Overall, only BP4_Supporting is met. Under the ENIGMA Table 3 combining rules, a single supporting benign criterion does not reach the threshold for Likely Benign (which requires either Strong_benign + Supporting_benign or >= 2 Supporting_benign). This variant is classified as a Variant of Uncertain Significance (VUS).⁶