ClinVar Miner

Submissions for variant NM_000206.2(IL2RG):c.982C>T (p.Arg328Ter) (rs1064793347)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000483975 SCV000565878 likely pathogenic not provided 2017-11-02 criteria provided, single submitter clinical testing The R328X nonsense variant in the IL2RG gene has been reported previously in association with immune deficiency (Chien et al., 2015; de Oliveira et al., 2015; Gallo et al., 2016); however, many of these individuals were presented in abstracted case reports and detailed information is not available. The variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). R328X results in truncation of the final 42 amino acids and is not predicted to result in nonsense-mediated decay. No downstream nonsense or missense variants have been reported in the Human Gene Mutation Database (Stenson et al., 2014). In summary, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
Integrated Genetics/Laboratory Corporation of America RCV000586219 SCV000695978 likely pathogenic X-linked severe combined immunodeficiency 2016-08-19 criteria provided, single submitter clinical testing Variant summary: The IL2RG c.982C>T (p.Arg328X) variant results in a premature termination codon, predicted to cause a truncated or absent IL2RG protein due to nonsense mediated decay, which are commonly known mechanisms for disease. One in silico tool predicts a damaging outcome for this variant. This variant is absent in 80559 control chromosomes. This variant has been reported in two brothers with a late-onset and atypical presentation of the disease via a conference abstract. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as likely pathogenic until more information becomes available.
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics RCV001090163 SCV001190359 pathogenic Combined immunodeficiency, X-linked 2020-03-06 criteria provided, single submitter clinical testing A hemizygous nonsense variation in exon 8 of the IL2RG gene that results in a stop codon and premature truncation of the protein at codon 328 was detected. The observed variant c.982C>T (p.Arg328Ter) has previously been reported in a patient affected with severe combined immunodeficiency (Luk ADW. et al., 2017). The variant has not been reported in the 1000 genomes and ExAC databases. The in silico prediction of the variant is damaging by MutationTaster2. The reference codon is conserved across mammals. In summary, the variant meets our criteria to be classified as pathogenic.

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