ClinVar Miner

Submissions for variant NM_000206.2(IL2RG):c.467C>T (p.Ala156Val) (rs1057521062)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000435698 SCV000520873 likely pathogenic not provided 2017-06-13 criteria provided, single submitter clinical testing The A156V variant has been published previously in association with X-linked SCID in a single patient (Ishii et al., 1994; Kumaki et al., 1999). The variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. A156V is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved; however, in silico analysis predicts this variant is probably damaging to the protein structure/function. Additionally, functional studies have shown that A156V has a detrimental effect on IL2RG protein localization and function (Ishii et al., 1994; Kumaki et al., 1999). Therefore, this variant is likely pathogenic.
Invitae RCV001235346 SCV001408027 likely pathogenic X-linked severe combined immunodeficiency 2019-11-13 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 156 of the IL2RG protein (p.Ala156Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) affected with X-linked severe combined immunodeficiency (PMID: 9885222, 8027558, Invitae). ClinVar contains an entry for this variant (Variation ID: 381532). This variant has been reported to affect IL2RG protein function (PMID: 9885222, 8027558). 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.