ClinVar Miner

Submissions for variant NM_002185.5(IL7R):c.704C>G (p.Ser235Ter)

dbSNP: rs766555082
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Total submissions: 3
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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 RCV000701107 SCV004102829 likely pathogenic Immunodeficiency 104 2023-11-14 reviewed by expert panel curation The c.704C>G (p.Ser235Ter)(NM_002185.5) variant in IL7R is a nonsense variant predicted to cause a premature stop codon in biologically-relevant-exon 5/8 leading to nonsense-mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). The variant has not been identified in the literature to our knowledge. In summary, this variant meets the criteria to be classified as likely pathogenic for SCID. ACMG/AMP criteria applied, as specified by the ClinGen SCID-VCEP: PVS1, PM2_Supporting. (VCEP specifications version 1).
Labcorp Genetics (formerly Invitae), Labcorp RCV000701107 SCV000829890 pathogenic Immunodeficiency 104 2018-01-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser235*) in the IL7R gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with IL7R-related disease. Loss-of-function variants in IL7R are known to be pathogenic (PMID: 21664875, 26123418). For these reasons, this variant has been classified as Pathogenic.
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego RCV000701107 SCV000996096 pathogenic Immunodeficiency 104 2017-12-29 criteria provided, single submitter clinical testing This stop-gain variant is predicted to result in premature termination of the IL7R protein. This variant has not been previously reported in the literature to our knowledge, but other pathogenic stop-gain changes have been reported in the literature in association with severe combined immunodeficiency (PMID: 15615257, 27807805). This variant is absent from population databases, thus is presumed to be rare. Based on the overall evidence, we classified the c.704C>G (p.Ser235Ter) variant as pathogenic.

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