ClinVar Miner

Submissions for variant NM_001370466.1(NOD2):c.2026C>T (p.Arg676Cys) (rs5743277)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000178334 SCV000230397 likely benign not specified 2014-10-24 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000330236 SCV000397256 likely benign Inflammatory bowel disease 1 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Clinical Services Laboratory,Illumina RCV000368536 SCV000397257 likely benign Blau syndrome 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000488013 SCV000575052 uncertain significance not provided 2016-09-01 criteria provided, single submitter clinical testing
Invitae RCV001086759 SCV000759547 likely benign Blau syndrome; Inflammatory bowel disease 1 2020-11-25 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001289749 SCV001477731 uncertain significance none provided 2019-12-17 criteria provided, single submitter clinical testing The NOD2 c.2107C>; p.Arg703Cys (rs5743277) variant has been described in the literature in individuals with autoinflammatory disease (Shen 2015, Yao 2012). The variant has also been described at an increased frequency in individuals with Crohn's disease and ulcerative colitis (Burillo-Sanz 2017, Lesage 2002, Rivas 2011). The variant is reported in the ClinVar database (Variation ID: 197333) and in the European (non-Finnish) population with an allele frequency of 0.5% (679/127436 alleles including 1 homozygote) in the Genome Aggregation Database. The arginine at codon 703 is moderately conserved and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. This variant may contribute to Crohn's disease as a risk factor, possibly together with other genetic and/or environmental factors. Although this variant has a population frequency incompatible with a periodic fever disease such as Blau syndrome, given the lack of clinical and functional data, the significance of the p.Arg703Cys variant is uncertain at this time. References: Burillo-Sanz et al. Mutational profile of rare variants in inflammasome-related genes in Behcet disease: A Next Generation Sequencing approach. Sci Rep. 2017 Aug 16;7(1):8453. Lesage et al. CARD15/NOD2 mutational analysis and genotype-phenotype correlation in 612 patients with inflammatory bowel disease. Am J Hum Genet. 2002 Apr;70(4):845-57 Rivas et al. Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease. Nat Genet. 2011 Oct 9;43(11):1066-73. Shen et al. Granulomatous disease associated with NOD2 sequence variants and familial camptodactyly: An intermediate form of NOD2-associated diseases? Semin Arthritis Rheum. 2015 Dec;45(3):357-60. Yao et al. Granulomatous pneumonitis associated with adult-onset Blau-like syndrome. Am J Respir Crit Care Med. 2012 Sep 1;186(5):465-6.

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