ClinVar Miner

Submissions for variant NM_000206.3(IL2RG):c.270-1G>T

dbSNP: rs193922346
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000030053 SCV000052708 likely pathogenic X-linked severe combined immunodeficiency 2011-08-18 criteria provided, single submitter curation Converted during submission to Likely pathogenic.
GeneDx RCV000430650 SCV000516115 pathogenic not provided 2015-03-30 criteria provided, single submitter clinical testing The c.270-1 G>T splice site variant in the IL2RG gene destroys the canonical spliceacceptor site in intron 2. It is predicted to cause abnormal gene splicing, either leading to an abnormal messagethat is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is usedfor protein translation. The c.270-1 G>T variant was not observed in approximately 6,500 individuals ofEuropean and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not acommon benign variant in these populations. We interpret the c.270-1 G>T variant as pathogenic.
Invitae RCV000030053 SCV002157078 pathogenic X-linked severe combined immunodeficiency 2021-03-22 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that disruption of this splice site results in altered mRNA splicing and is expected to lead to the loss of protein expression (PMID: 28359783). Disruption of this splice site ‚Äãhas been observed in individual(s) with severe combined immunodeficiency (PMID: 28359783, Invitae). ClinVar contains an entry for this variant (Variation ID: 36384) This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor 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).

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