ClinVar Miner

Submissions for variant NM_000536.4(RAG2):c.1367C>A (p.Ala456Asp)

gnomAD frequency: 0.00001  dbSNP: rs1479440369
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001300504 SCV001489647 uncertain significance Combined immunodeficiency with skin granulomas; Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive 2021-08-28 criteria provided, single submitter clinical testing This sequence change replaces alanine with aspartic acid at codon 456 of the RAG2 protein (p.Ala456Asp). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with RAG2-related conditions. 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. 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. RCV001835435 SCV002090411 uncertain significance Histiocytic medullary reticulosis 2021-02-18 no assertion criteria provided clinical testing

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