ClinVar Miner

Submissions for variant NM_022162.3(NOD2):c.2722G>C (p.Gly908Arg) (rs2066845)

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Total submissions: 6
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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 RCV000238745 SCV000297307 uncertain significance not specified 2015-11-11 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000363061 SCV000397297 likely benign Crohn disease 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000268347 SCV000397298 likely benign Blau syndrome 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000638041 SCV000759521 risk factor Blau syndrome; Inflammatory bowel disease 1 2018-12-31 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 908 of the NOD2 protein (p.Gly908Arg). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs2066845, ExAC 1.4%), including multiple homozygous individuals. Numerous population-based case-control studies have shown that this variant confers an elevated risk of Crohn's disease (PMID: 21548950, 15024686, 18489434, 15190267, 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 = 2.6, 95% CI 2.2-2.9). 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 known as G881R in the literature. ClinVar contains an entry for this variant (Variation ID: 4692). Experimental studies have shown that this missense change results in decreased NFkB activity and decreased response to lipopolysaccharide and peptidoglycan compared to wildtype protein (PMID: 12512038, 15198989). In summary, this is a frequently observed variant that is associated with approximately a 2.6-fold increased risk of Crohn's disease in population studies. Therefore, it has been classified as an Increased Risk Allele.
OMIM RCV000004956 SCV000025132 risk factor Inflammatory bowel disease 1 2002-07-01 no assertion criteria provided literature only
OMIM RCV000416490 SCV000494280 risk factor Yao syndrome 2002-07-01 no assertion criteria provided literature only

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