ClinVar Miner

Submissions for variant NM_000536.4(RAG2):c.1526G>T (p.Gly509Val)

gnomAD frequency: 0.00001  dbSNP: rs779267024
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000756589 SCV000884445 uncertain significance not provided 2017-09-25 criteria provided, single submitter clinical testing The p.Gly509Val variant (rs779267024) has not been reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. This variant is listed in the genome Aggregation Database (gnomAD) on 2 chromosomes (2 out of 246,182 chromosomes).The glycine at position 509 is moderately conserved (Alamut v.2.10.0) and computational analyses of the effects of the p.Gly509Val variant on protein structure and function provide conflicting results (SIFT: tolerated, MutationTaster: disease causing, PolyPhen-2: benign). Altogether, there is not enough evidence to classify the p.Gly509Val variant with certainty.
Invitae RCV001322463 SCV001513337 uncertain significance Combined immunodeficiency with skin granulomas; Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive 2022-04-04 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 509 of the RAG2 protein (p.Gly509Val). This variant is present in population databases (rs779267024, gnomAD 0.002%). 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: 618341). 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 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.
Ambry Genetics RCV002533123 SCV003540499 uncertain significance Inborn genetic diseases 2022-11-07 criteria provided, single submitter clinical testing The c.1526G>T (p.G509V) alteration is located in exon 2 (coding exon 1) of the RAG2 gene. This alteration results from a G to T substitution at nucleotide position 1526, causing the glycine (G) at amino acid position 509 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001825494 SCV002090333 uncertain significance Histiocytic medullary reticulosis 2020-09-11 no assertion criteria provided clinical testing

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