Submissions for variant NM_001370466.1(NOD2):c.2465C>T (p.Ala822Val)

gnomAD frequency: 0.00003  dbSNP: rs104895486

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000381377	SCV000397283	likely benign	Blau syndrome	2017-04-28	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). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV001781423	SCV000397284	likely benign	Inflammatory bowel disease 1	2017-04-28	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.
Invitae	RCV002513882	SCV000948663	uncertain significance	Blau syndrome; Regional enteritis	2023-11-01	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 849 of the NOD2 protein (p.Ala849Val). This variant is present in population databases (rs104895486, gnomAD 0.04%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with Crohn's disease (PMID: 16485124). ClinVar contains an entry for this variant (Variation ID: 97855). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002260983	SCV002542700	likely benign	Autoinflammatory syndrome	2020-11-11	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV003736574	SCV004563540	uncertain significance	not provided	2023-10-20	criteria provided, single submitter	clinical testing	The NOD2 c.2546C>T; p.Ala849Val variant (rs104895486) is reported in the literature in an individual with Crohn's disease (Schnitzler 2006). This variant is also reported in ClinVar (Variation ID: 97855). It is observed in the general population with an overall allele frequency of 0.008% (20/251148 alleles) in the Genome Aggregation Database. Computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.226). Due to limited information, the clinical significance of this variant is uncertain at this time. References: Schnitzler F et al. Eight novel CARD15 variants detected by DNA sequence analysis of the CARD15 gene in 111 patients with inflammatory bowel disease. Immunogenetics. 2006 Apr;58(2-3):99-106. PMID: 16485124.
Unité médicale des maladies autoinflammatoires, CHRU Montpellier	RCV000381377	SCV000116243	not provided	Blau syndrome		no assertion provided	not provided