NM_177438.2:c.1282G>C (p.Glu428Gln) is a missense variant in exon 8 of DICER1, located in the N-terminal DExD helicase domain, outside the RNase IIIb domain and metal ion-binding hotspot residues.¹ The variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada, meeting the DICER1 VCEP PM2_Supporting criterion (AF < 0.000005).² Computational evidence suggests a benign effect: REVEL score is 0.186 (< 0.500), BayesDel score is -0.262, and SpliceAI predicts no splicing impact (max delta = 0.00), meeting the DICER1 VCEP BP4_Supporting criterion.³ The variant has been observed once in somatic cancers (COSMIC COSV100602630) but has not been reported in ClinVar or the germline literature.⁴ No functional data, de novo observations, family segregation data, or tumor sequencing data are available to assess PS3, PS2, PP1, or PP4. Under the DICER1 VCEP v1.4 Tavtigian point-based system: PM2_Supporting (+1) + BP4_Supporting (-1) = 0 points, classifying this variant as a Variant of Uncertain Significance.⁵