NM_000251.3:c.2458+8C>G is an intronic variant in MSH2 located at position +8 of intron 14. SpliceAI predicts no splicing impact (max delta score 0.04), satisfying BP4 at Supporting benign strength per the InSiGHT MSH2 VCEP v2.0.0.¹ This variant is present in gnomAD v4.1 at a low frequency (33/1,613,836 alleles; AF=2.04e-05; grpmax FAF=8.99e-05) but does not meet the VCEP PM2 threshold (<0.00002) nor BS1 (≥0.0001), falling in an intermediate frequency range that neither supports nor refutes pathogenicity under VCEP rules.² As an intronic variant at position +8 (beyond the +7 boundary), BP7 applies at Supporting benign strength per VCEP rules. The variant may satisfy both BP7 and BP4.³ This variant has been reported in ClinVar (ClinVar ID 135857) as Likely benign by 10 clinical laboratories and as Benign by 1 clinical laboratory, with no expert panel review to date. No published studies have specifically evaluated this variant for functional effects, segregation, or tumor phenotype.⁴ No evidence is available for PVS1 (not a null variant), PS2 (no de novo reports), PS3 (no functional studies), PP1 (no segregation data), PP4 (no tumor MSI/IHC data), BS2 (no trans co-occurrence), BS3 (no laboratory functional assay), BS4 (no lack-of-segregation data), or BP5 (no tumor phenotype data).⁵ Applying the InSiGHT MSH2 VCEP v2.0.0 combining rules: two Supporting benign criteria (BP4 + BP7) are met, satisfying Rule 19 (≥2 Benign Supporting → Likely Benign).⁶