ClinVar Miner

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

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Total submissions: 2
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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.

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