ClinVar Miner

Submissions for variant NM_000536.4(RAG2):c.14T>A (p.Met5Lys)

gnomAD frequency: 0.00019  dbSNP: rs143415103
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000330271 SCV000371808 uncertain significance Histiocytic medullary reticulosis 2016-06-14 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV001731472 SCV000371809 uncertain significance Severe combined immunodeficiency disease 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000689525 SCV000817179 uncertain significance Combined immunodeficiency with skin granulomas; Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive 2022-08-16 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with lysine, which is basic and polar, at codon 5 of the RAG2 protein (p.Met5Lys). This variant is present in population databases (rs143415103, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with RAG2-related conditions. ClinVar contains an entry for this variant (Variation ID: 304560). 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 expected to disrupt RAG2 protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
Natera, Inc. RCV000330271 SCV001458525 uncertain significance Histiocytic medullary reticulosis 2020-03-11 no assertion criteria provided clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV001528918 SCV001741486 uncertain significance not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV001528918 SCV001965608 uncertain significance not provided no assertion criteria provided clinical testing

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