ClinVar Miner

Submissions for variant NM_000206.3(IL2RG):c.115+2T>C

dbSNP: rs2147751760
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
ClinGen Severe Combined Immunodeficiency Variant Curation Expert Panel, ClinGen RCV001867748 SCV004102797 pathogenic X-linked severe combined immunodeficiency 2023-11-14 reviewed by expert panel curation The c.115+2T>C (NM_000206.3) variant in IL2RG occurs within the canonical donor splice site in intron 1. It is expected to disrupt RNA splicing, disrupting the reading frame, and is predicted to undergo NMD. (PVS1). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). At least one patient was found in the literature showing: XY male sex (0.5pts) + T-B+NK- lymphocyte subset profile (0.5pt), total 1 point, PP4_Supporting. (PMID: 9058718; Puck JM et al). In summary, this variant meets the criteria to be classified as Pathogenic for SCID based on the ACMG/AMP criteria applied: PVS1, PP4_Supporting, and PM2_Supporting, as specified by the ClinGen SCID VCEP specifications version 1.
Labcorp Genetics (formerly Invitae), Labcorp RCV001867748 SCV002136328 pathogenic X-linked severe combined immunodeficiency 2022-08-15 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 1368945). This variant is also known as 129(+2). Disruption of this splice site has been observed in individuals with severe combined immunodeficiency (PMID: 9058718). This sequence change affects a donor splice site in intron 1 of the IL2RG gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in IL2RG are known to be pathogenic (PMID: 9058718, 10794430).

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.