ClinVar Miner

Submissions for variant NM_002185.5(IL7R):c.265C>T (p.Gln89Ter)

gnomAD frequency: 0.00001  dbSNP: rs141698985
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Total submissions: 5
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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 RCV001869366 SCV004098871 likely pathogenic Immunodeficiency 104 2023-10-10 reviewed by expert panel curation The NM_002185.5(IL7R):c.265C>T (p.Gln89Ter) variant in IL7R is a nonsense variant predicted to cause a premature stop codon in biologically-relevant-exon 3/8, which is predicted to lead to nonsense-mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). The filtering allele frequency based on the European (non-Finnish) population (upper bound of 95% CI of 3/113430 alleles) is 0.000007030 in gnomAD v2.1.1, which is below the SCID-VCEP threshold (<0.00004129; PM2_Supporting). This variant has been reported in ClinVar and LOVD without patient information; however, it has not been reported in the literature to our knowledge. In summary, this variant meets the criteria to be classified as Likely Pathogenic for autosomal recessive SCID based on the ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP. Criteria applied: PVS1, PM2_supporting (SCID VCEP specifications version 1.0).
Molecular Diagnostics Laboratory, M Health Fairview: University of Minnesota RCV000991308 SCV001142712 likely pathogenic Histiocytic medullary reticulosis 2019-07-03 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001726410 SCV001961872 pathogenic not provided 2021-09-01 criteria provided, single submitter clinical testing
Invitae RCV001869366 SCV002234621 pathogenic Immunodeficiency 104 2023-06-09 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 804345). This variant has not been reported in the literature in individuals affected with IL7R-related conditions. This variant is present in population databases (rs141698985, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Gln89*) in the IL7R gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in IL7R are known to be pathogenic (PMID: 21664875, 26123418).
PreventionGenetics, part of Exact Sciences RCV003898007 SCV004709053 likely pathogenic IL7R-related disorder 2024-02-28 criteria provided, single submitter clinical testing The IL7R c.265C>T variant is predicted to result in premature protein termination (p.Gln89*). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0026% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Nonsense variants in IL7R are expected to be pathogenic. This variant is interpreted as likely pathogenic.

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