ClinVar

Description

This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 110 of the NPR2 protein (p.Arg110Cys). This variant is present in population databases (rs758478717, gnomAD 0.0009%). This missense change has been observed in individual(s) with autosomal recessive acromesomelic dysplasia (PMID: 24471569, 33288834). ClinVar contains an entry for this variant (Variation ID: 208359). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt NPR2 protein function. Experimental studies have shown that this missense change affects NPR2 function (PMID: 24471569). This variant disrupts the p.Arg110 amino acid residue in NPR2. Other variant(s) that disrupt this residue have been observed in individuals with NPR2-related conditions (PMID: 33288834, 35368703), which suggests that this may be a clinically significant amino acid residue. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.