Submissions for variant NM_001370466.1(NOD2):c.2251G>A (p.Glu751Lys)

gnomAD frequency: 0.00020  dbSNP: rs104895443

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV002514478	SCV000759538	likely benign	Blau syndrome; Regional enteritis	2023-12-09	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001781418	SCV000914721	uncertain significance	Inflammatory bowel disease 1	2018-03-09	criteria provided, single submitter	clinical testing	The NOD2 c.2332G>A (p.Glu778Lys) variant has been reported in three studies and is found in a total of two patients with Crohn disease in a heterozygous state and an additional three patient alleles (zygosity not specified) (Lesage et al. 2002; Sun et al. 2003; Lakatos et al. 2005). The p.Glu778Lys variant was reported in one of 404 controls in a heterozygous state and is reported at a frequency of 0.000490 in the European (non-Finnish) population of the Genome Aggregation Database. The Glu778 residue is conserved. Functional studies showed that the p.Glu778Lys variant exhibits reduced PGN-dependent response in HEK293 cells and impaired recognition of bacterial muramyl dipeptide derived from bacterial peptidoglycan. A breakdown in tolerance to luminal bacteria is suggested as an etiology for Crohn disease (Chamaillard et al. 2003; Tanabe et al. 2004). The evidence for this variant is limited. The p.Glu778Lys variant is therefore classified as a variant of unknown significance but suspicious for pathogenicity for Crohn disease. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Genomic Research Center, Shahid Beheshti University of Medical Sciences	RCV000785151	SCV000923714	uncertain significance	not specified	2019-01-01	criteria provided, single submitter	clinical testing
Baylor-Hopkins Center for Mendelian Genomics, Johns Hopkins University School of Medicine	RCV001781418	SCV000924194	uncertain significance	Inflammatory bowel disease 1		criteria provided, single submitter	research
Illumina Laboratory Services, Illumina	RCV000084105	SCV001276794	likely benign	Blau syndrome	2018-03-08	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.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002260978	SCV002542684	uncertain significance	Autoinflammatory syndrome	2021-11-29	criteria provided, single submitter	clinical testing
Unité médicale des maladies autoinflammatoires, CHRU Montpellier	RCV000084105	SCV000116236	not provided	Blau syndrome		no assertion provided	not provided