NM_000251.3:c.2001_2002del is a 2-bp deletion in exon 12 of MSH2 that causes a frameshift (p.Thr668TrpfsTer7) and introduces a premature termination codon at position 674, well before the InSiGHT VCEP PVS1_VeryStrong cutoff of codon 891.¹ The variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada, meeting PM2_Supporting under InSiGHT VCEP criteria (allele frequency <0.00002).² The variant is absent from ClinVar and has not been reported in COSMIC; no published case reports or functional studies specific to this variant were identified in the five publications reviewed.³ Applying the InSiGHT MMR VCEP v2.0 combining rules: one Pathogenic Very Strong criterion (PVS1) plus one Pathogenic Supporting criterion (PM2) meets Rule 10 for Likely Pathogenic (1 Very Strong + 1 Moderate, but PM2 is only Supporting in this VCEP, so the classification defaults to Rule 10: 1 Very Strong + 1 Moderate = Likely Pathogenic; however PM2_Supporting alone with PVS1 does not reach a second moderate — the classification resolves under Rule 1: ≥1 Very Strong = Pathogenic).⁴