Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV002222990 | SCV002500454 | likely pathogenic | X-linked severe combined immunodeficiency | 2022-03-18 | 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. This variant is also known as 189G>T in HGVS. Truncations downstream of this position have been classified as pathogenic by our laboratory. Truncations downstream of this position are also associated with Severe Combined Immunodeficiency in HGMD. The variant was absent in 174848 control chromosomes (gnomAD). 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |