ClinVar Miner

Submissions for variant NM_000448.3(RAG1):c.2459A>G (p.Lys820Arg)

gnomAD frequency: 0.12928  dbSNP: rs2227973
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Total submissions: 12
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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 RCV003492019 SCV004242264 benign Recombinase activating gene 1 deficiency 2024-01-23 reviewed by expert panel curation The NM_000448.3:c.2459A>G variant in RAG1 is a missense variant predicted to cause the substitution of Lysine by Arginine at amino acid 820 (p.Lys820Arg). The filtering allele frequency (the lower threshold of the 95% CI of 26338/44862) of the c.2459A>G variant in RAG1 is 0.5818 for East Asian chromosomes by gnomAD v.4, which is higher than the ClinGen SCID VCEP threshold (>0.00872) for BA1, and therefore meets this criterion (BA1). Additionally, 22786 homozygous adults are reported on gnomAD v.4, BS2_Supporting is Met. In summary, this variant meets the criteria to be classified as Benign for autosomal recessive SCID. ACMG/AMP criteria applied, as specified by the ClinGen SCID-VCEP: BA1 and BS2_Supporting. (VCEP specifications version 1).
Preventiongenetics, part of Exact Sciences RCV000245314 SCV000304366 benign not specified criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000385043 SCV000371686 benign Histiocytic medullary reticulosis 2018-03-06 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina RCV000290555 SCV000371687 benign Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive 2018-03-06 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000245314 SCV000540148 benign not specified 2016-03-28 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency - papers in HGMD do not provide evidence of disease association
Invitae RCV001512872 SCV001720364 benign Combined immunodeficiency with skin granulomas; Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive 2024-02-01 criteria provided, single submitter clinical testing
GeneDx RCV001636747 SCV001852445 benign not provided 2015-03-03 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 16857995, 24290284, 22424479, 21625022)
Genome-Nilou Lab RCV001795396 SCV002033423 benign Combined immunodeficiency with skin granulomas 2021-11-07 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000385043 SCV002033424 benign Histiocytic medullary reticulosis 2021-11-07 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000290555 SCV002033425 benign Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive 2021-11-07 criteria provided, single submitter clinical testing
GreenArray Genomic Research & Solutions of Accurate Diagnostic Private Limited RCV001814976 SCV002061920 benign Immunodeficiency 104 criteria provided, single submitter clinical testing The variant is predicted to be benign by PolyPhen2 and the residue is conserved across species. The amino acid change p.Lys820Arg in RAG1
Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan RCV000245314 SCV004233912 benign not specified 2024-01-24 criteria provided, single submitter clinical testing This variant is classified as Benign based on local population frequency. This variant was detected in 48% of patients studied by a panel of primary immunodeficiencies. Number of patients: 42. Only high quality variants are reported.

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