NM_001127208.2:c.2152delC is a frameshift deletion predicted to result in premature termination at codon 751 (p.Leu718PhefsTer33) in TET2, a gene for which heterozygous germline loss-of-function variants are an established cause of an autoimmune lymphoproliferative syndrome-like phenotype and hematologic malignancy.¹ This variant is absent from gnomAD population databases (v2.1 exomes, v4.1 exomes/genomes, and gnomAD-Canada v1.0), indicating it is not a common benign polymorphism and supporting evidence for rarity in the general population.² Under the generic ACMG/AMP 2015 classification framework, application of PVS1 (Very Strong) for a null variant in a gene where loss of function is a known disease mechanism, together with PM2 (Moderate) for absence from population databases, yields a Likely Pathogenic classification (1 Very Strong + 1 Moderate).³