ClinVar Miner

Submissions for variant NM_000206.2(IL2RG):c.903_910del (p.Glu302fs) (rs1556329779)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000556829 SCV000637254 pathogenic X-linked severe combined immunodeficiency 2017-05-16 criteria provided, single submitter clinical testing This sequence change deletes 8 nucleotides from exon 7 of the IL2RG mRNA (c.903_910delTGAATACC), causing a frameshift at codon 302. This creates a premature translational stop signal in the last exon of the IL2RG mRNA (p.Glu302Argfs*11). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 66 amino acids of the IL2RG protein. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with an IL2RG-related disease. While the effect of this particular variant has not been studied, it is expected to disrupt the C-terminal region of the interleukin receptor common gamma chain, which is known to be critical for proper association with Jak3 (PMID: 7973658, 7973659). Deletions affecting this intracellular region of the protein have been shown to lead to defects in signal transduction, including loss of ability to induce c-myc, c-fos, and c-jun expression (PMID: 7683423). In summary, this is a novel truncation that disrupts a protein domain that is essential for proper IL2 receptor function. Therefore this variant has been classified as 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.