ClinVar Miner

Submissions for variant NM_000206.3(IL2RG):c.269+1G>T

dbSNP: rs2092262300
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
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 RCV001863206 SCV004809093 pathogenic X-linked severe combined immunodeficiency 2024-01-30 reviewed by expert panel curation The c.269+1G>T (NM_000206.3) variant in IL2RG occurs within the canonical donor splice site (+1) of intron 2. The variant is predicted by SpliceAI to affect splicing. It is expected to cause skipping of a biologically relevant exon 2 resulting in a frameshift (p.Asp39Glyfs*57) leading to nonsense mediated decay in a gene in which loss of function is an established disease mechanism (PVS1). The variant is absent in gnomAD v4 (PM2_supporting). Male patient (0.5 pt.) with SCID (0.5 pt.), genome sequencing conducted (1 pt.), T-B+NK- lymphocyte subset profile (0.5 pt.); total :2.5 pts (PP4_Moderate) PMID: 33628209. In summary, this variant meets the criteria to be classified as a Pathogenic variant for X-linked severe combined immunodeficiency due to IL2RG deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP: PVS1,PM2_supporting,PP4_Moderate (VCEP specifications version 1).
Baylor Genetics RCV001329693 SCV001521204 likely pathogenic Combined immunodeficiency, X-linked 2020-06-10 criteria provided, single submitter clinical testing This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
Labcorp Genetics (formerly Invitae), Labcorp RCV001863206 SCV002242714 pathogenic X-linked severe combined immunodeficiency 2021-10-30 criteria provided, single submitter clinical testing 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: 1028611). Disruption of this splice site has been observed in individual(s) with severe combined immunodeficiency (PMID: 9058718, 33628209). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 2 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.