ClinVar Miner

Submissions for variant NM_022162.2(NOD2):c.2104C>T (p.Arg702Trp) (rs2066844)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000203217 SCV000258186 uncertain significance not specified 2015-04-17 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000365422 SCV000397254 likely benign Blau syndrome 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000273268 SCV000397255 likely benign Crohn disease 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000536287 SCV000636098 risk factor Blau syndrome; Inflammatory bowel disease 1 2018-07-03 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 702 of the NOD2 protein (p.Arg702Trp). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs2066844, ExAC 3%), including multiple homozygous individuals. Numerous population-based case-control studies have shown that this variant confers an elevated risk of Crohn's disease (PMID: 11385576, 21548950, 18489434, 21274544, 15770725, 15024686, 15571588). In a large meta-analysis involving 75 case-control studies with 18,727 cases and 17,102 controls (PMID: 19713276), individuals carrying this variant had an increased overall risk of Crohn's disease (OR = 2.2, 95% CI 2.0-2.5). When all three NOD2 genotypes were combined (p.Arg702Trp, p.Gly908Arg, and p.Leu1007Profs*2), the odds ratios for Crohn's disease were 2.4 (95% CI, 2.0-2.8) for simple heterozygotes, 9.0 (95% CI 6.0-13.5) for compound heterozygotes, and 6.7 (95% CI 4.1-10.9) for homozygotes, compared with noncarriers. This variant is also referred to as R675W and SNP8 in the literature. ClinVar contains an entry for this variant (Variation ID: 4693). Experimental studies have shown that this missense change results in decreased NFkB activity and decreased response to lipopolysaccharide, muramyl dipeptide, and peptidoglycan compared to wildtype protein (PMID: 12512038, 15198989, 18240302, 22684479). In summary, this is a frequently observed variant that is associated with approximately a 2.2-fold increased risk of Crohn's disease in population studies. Therefore, it has been classified as an Increased Risk Allele.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000203217 SCV000539927 benign not specified 2016-03-29 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
OMIM RCV000004957 SCV000025133 risk factor Inflammatory bowel disease 1 2002-07-01 no assertion criteria provided literature only
OMIM RCV000416493 SCV000494281 risk factor Yao syndrome 2002-07-01 no assertion criteria provided literature only

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