ClinVar Miner

Submissions for variant NM_002185.5(IL7R):c.707G>A (p.Gly236Glu)

gnomAD frequency: 0.00023  dbSNP: rs201084372
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000927648 SCV000457151 uncertain significance Immunodeficiency 104 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae RCV000927648 SCV001073236 benign Immunodeficiency 104 2024-01-31 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003479106 SCV004222931 likely benign not specified 2023-11-20 criteria provided, single submitter clinical testing Variant summary: IL7R c.707G>A (p.Gly236Glu) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. Consensus agreement among computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00022 in 1602544 control chromosomes, predominantly at a frequency of 0.0089 within the Ashkenazi Jewish subpopulation in the gnomAD database (v4.0), including 4 homozygotes. The observed variant frequency within Ashkenazi Jewish control individuals in the gnomAD database is approximately 8-fold of the estimated maximal expected allele frequency for a pathogenic variant in IL7R causing Severe Combined Immunodeficiency phenotype (0.0011), suggesting that the variant may be a benign polymorphism found primarily in populations of Ashkenazi Jewish origin. To our knowledge, no occurrence of c.707G>A in individuals affected with Severe Combined Immunodeficiency and no experimental evidence demonstrating its impact on protein function have been reported. Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. One submitter classified the variant as benign, and one submitter classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign.

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