NM_000535.7:c.2566C>T (p.Leu856=) is a synonymous variant in exon 15 of PMS2. It is extremely rare in population databases, with an allele frequency of 5.057e-06 in gnomAD v4.1 (5/988,724 alleles, no homozygotes) and absent from gnomAD v2.1, satisfying PM2_Supporting per PMS2 VCEP v2.0.0.¹ SpliceAI predicts no splicing impact for this variant (max delta = 0.00), satisfying BP4_Supporting per PMS2 VCEP v2.0.0 for synonymous variants.² The variant is a synonymous substitution located at c.2566 in exon 15, +120 nucleotides from the splice acceptor site, well beyond the +7 position defined by the BP7 rule. BP7_Supporting is met per PMS2 VCEP v2.0.0.³ PVS1, PS1, and PM5 are not applicable as this is a synonymous variant producing no amino acid change. PS4, PM1, PM6, PP2, PP5, BP1, BP2, and BP6 are not applicable per the PMS2 VCEP v2.0.0 specifications.⁴ No de novo observations (PS2), functional studies (PS3, BS3), cosegregation data (PP1, BS4), trans co-occurrence data (BS2), tumor pathology data (PP4, BP5), or computational evidence supporting pathogenicity (PP3) were identified for this variant. This variant has been reported in ClinVar as Likely benign by four clinical laboratories and Benign by one clinical laboratory (ClinVar ID 701564). In ClinVar, submissions cited methodology papers without variant-specific clinical evidence.⁵ Under the PMS2 VCEP v2.0.0 combination rules, the presence of two benign supporting criteria (BP4_Supporting, BP7_Supporting) satisfies Rule19 (>=2 Benign.Supporting -> Likely Benign). PM2_Supporting is also met but does not alter the classification under the VCEP rule hierarchy.⁶