ClinVar Miner

Submissions for variant NM_022162.3(NOD2):c.2555A>G (p.Asn852Ser) (rs104895467)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000280478 SCV000329195 uncertain significance not provided 2016-03-14 criteria provided, single submitter clinical testing The N852S variant in the NOD2 gene has been reported in several publications as a rare risk allele associated with Crohn disease in the Ashkenazi Jewish population (Tukel et al., (2004); King et al. (2006); Rivas et al., (2011); Zhang W et al., 2013). The NHLBI ESP Exome Sequencing Project reports N852S was observed with a frequency of 0.11% in 10/8600 alleles from individuals of European background, indicating it may be a rare (benign) variant in this population. The N852S variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret N852S in NOD2 as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV000281894 SCV000397287 likely benign Crohn disease 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000336827 SCV000397288 likely benign Blau syndrome 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000638061 SCV000759541 risk factor Blau syndrome; Inflammatory bowel disease 1 2018-12-30 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 852 of the NOD2 protein (p.Asn852Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs104895467, ExAC 0.2%) including at least one homozygous individual. In a large association analysis involving over 40,000 cases and controls (PMID: 21983784), individuals who carried this variant had a significantly increased risk of Crohn's disease (OR=2.47, 95% CI=1.55-3.93). ClinVar contains an entry for this variant (Variation ID: 97856). Experimental studies have shown that while this missense change does not interfere with normal membrane localization, it impairs MDP-induced NF-kB activation (PMID: 21983784). In summary, this is a frequently observed variant that is associated with an approximately 2.5-fold increased risk for developing Crohn's disease.
Unité médicale des maladies autoinflammatoires, CHRU Montpellier RCV000084113 SCV000116244 not provided Sarcoidosis, early-onset no assertion provided not provided

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