ClinVar Miner

Submissions for variant NM_000206.3(IL2RG):c.175G>T (p.Glu59Ter)

dbSNP: rs2092262517
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Severe Combined Immunodeficiency Variant Curation Expert Panel, ClinGen RCV002222990 SCV005375412 likely pathogenic X-linked severe combined immunodeficiency 2024-06-12 reviewed by expert panel curation The c.175G>T (p.Glu59Ter) (NM_000206.3) variant in IL2RG is a nonsense variant predicted to cause a premature stop codon in biologically-relevant-exon 2/8 leading to nonsense-mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1 Met).The variant is absent in gnomAD v4 (PM2_supporting). There are no publications for this variant in the literature. In summary, this variant meets the criteria to be classified as a Likely 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_Met, PM2_supporting (VCEP specifications version 1).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002222990 SCV002500454 pathogenic X-linked severe combined immunodeficiency 2025-02-24 criteria provided, single submitter clinical testing Variant summary: IL2RG c.175G>T (p.Glu59X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The frequency data for this variant in gnomAD is considered unreliable, as metrics indicate poor data quality at this position. To our knowledge, no occurrence of c.175G>T in individuals affected with X-Linked Severe Combined Immunodeficiency and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 1677132). Based on the evidence outlined above, the variant was classified as pathogenic.

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