ClinVar Miner

Submissions for variant NM_001370466.1(NOD2):c.2446G>A (p.Glu816Lys)

gnomAD frequency: 0.00008  dbSNP: rs104895445
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV002514479 SCV001538039 uncertain significance Blau syndrome; Regional enteritis 2024-01-22 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 843 of the NOD2 protein (p.Glu843Lys). This variant is present in population databases (rs104895445, gnomAD 0.02%). This missense change has been observed in individual(s) with Crohn's disease (PMID: 11875755). ClinVar contains an entry for this variant (Variation ID: 97854). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt NOD2 protein function with a negative predictive value of 95%. Experimental studies have shown that this missense change affects NOD2 function (PMID: 12626759). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV001753486 SCV001987703 uncertain significance not provided 2020-06-05 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Reported in association with susceptibility to Crohn disease in one patient in published literature, but it is unknown if this individual was screened for variants in other genes associated with the phenotype (Lesage et al., 2002); This variant is associated with the following publications: (PMID: 11875755)
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV002260982 SCV002542699 uncertain significance Autoinflammatory syndrome 2018-09-01 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001753486 SCV003799594 uncertain significance not provided 2022-04-01 criteria provided, single submitter clinical testing The NOD2 c.2527G>A; p.Glu843Lys variant (rs104895445), is reported in the literature in an individual affected with Chron's disease (Lesage, 2002). This variant is found in the general population with an overall allele frequency of 0.008 % (23/282,748 alleles) in the Genome Aggregation Database. The glutamic acid at codon 843 is highly conserved, but computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.19). Due to limited information, the clinical significance of the p.Glu843Lys variant is uncertain at this time. References: Lesage S 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. PMID: 11875755.
Unité médicale des maladies autoinflammatoires, CHRU Montpellier RCV000084111 SCV000116242 not provided Blau syndrome no assertion provided not provided

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