The NM_002524.5:c.34G>A variant in NRAS is a missense variant predicted to cause substitution of glycine by serine at amino acid 12 (p.Gly12Ser). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). The computational predictor REVEL gives a score of 0.612, which is neither above nor below the thresholds predicting a damaging or benign impact on NRAS function. This variant occurs at an amino acid residue defined by the ClinGen RASopathy VCEP as an amino acid residue where ≥2 different [likely] pathogenic residues changes at the same codon have been observed in ≥5 probands (PM5_Strong). This variant has been reported in 4 probands with RASopathy (PS4_Moderate; PMIDs: 26918529, 28098151, 28594414, SCV00028917.11, GeneDx). This variant has been identified as a de novo occurrence with confirmed parental relationships in 1 individual and as a de novo occurrence with unconfirmed parental relationships in 2 individuals with RASopathy (PS2_VeryStrong; PMIDs: 28098151 and 28594414, SCV000208917.11, GeneDx). In summary, this variant meets the criteria to be classified as pathogenic for autosomal dominant RASopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen RASopathy VCEP: PS2_VeryStrong, PM5_Strong, PS4_Moderate, PM2_Supporting. (ClinGen RASopathy VCEP specifications version 2.1; 9/17/2024)