Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001966612 | SCV002247751 | likely pathogenic | X-linked severe combined immunodeficiency | 2021-11-09 | criteria provided, single submitter | clinical testing | This variant disrupts the p.Cys182 amino acid residue in IL2RG. Other variant(s) that disrupt this residue have been observed in individuals with IL2RG-related conditions (PMID: 10794430, 18728247), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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 IL2RG protein function. This missense change has been observed in individual(s) with severe combined immunodeficiency (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with serine, which is neutral and polar, at codon 182 of the IL2RG protein (p.Cys182Ser). |