ClinVar Miner

Submissions for variant NM_002185.5(IL7R):c.214G>C (p.Glu72Gln)

gnomAD frequency: 0.00038  dbSNP: rs148001159
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000030059 SCV000052714 uncertain significance not specified 2019-11-19 criteria provided, single submitter clinical testing Variant summary: IL7R c.214G>C (p.Glu72Gln) results in a conservative amino acid change located in the IL-7Ralpha, fibronectin type III domain (IPR040997) of the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00024 in 251020 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in IL7R causing Severe Combined Immunodeficiency Syndrome (0.00024 vs 0.0013), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.214G>C in individuals affected with Severe Combined Immunodeficiency Syndrome and no experimental evidence demonstrating an impact on protein function have been reported. Two other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Both laboratories cited the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Illumina Laboratory Services, Illumina RCV000813303 SCV000457140 uncertain significance Immunodeficiency 104 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Invitae RCV000813303 SCV000953660 uncertain significance Immunodeficiency 104 2022-10-17 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 72 of the IL7R protein (p.Glu72Gln). This variant is present in population databases (rs148001159, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with IL7R-related conditions. ClinVar contains an entry for this variant (Variation ID: 36390). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt IL7R protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics RCV000813303 SCV002781298 uncertain significance Immunodeficiency 104 2022-05-05 criteria provided, single submitter clinical testing

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