ClinVar Miner

Submissions for variant NM_001370466.1(NOD2):c.2296G>A (p.Val766Met) (rs104895444)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000405468 SCV000397272 likely benign Inflammatory bowel disease 1 2018-03-06 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Invitae RCV001080854 SCV001100921 likely benign Blau syndrome; Inflammatory bowel disease 1 2019-12-31 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000954298 SCV001150914 likely benign not provided 2017-12-01 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001001762 SCV001159379 uncertain significance not specified 2019-01-25 criteria provided, single submitter clinical testing The NOD2 c.2377G>A; p.Val793Met variant (rs104895444) has been reported in association with inflammatory bowel disease (Huang 2017, Lesage 2002, Rivas 2011), but to our knowledge, has not been reported in an individual with Blau syndrome. In general, gain-of-function missense variants in the NACHT domain (amino residues 273-617) have been reported in association with Blau syndrome. The variant has been reported to function like wild-type in cell culture (Chamaillard 2003). The variant is reported as likely benign by a reputable database (see link below) and has been reported as likely benign in the ClinVar database (Variation ID: 97851). The variant is reported in the general population with an allele frequency of 0.1% (322/280848 alleles, including 2 homozygotes) in the Genome Aggregation Database. The valine at this position is highly conserved but computational analyses (SIFT: Damaging, PolyPhen-2: Benign) predict conflicting effects of this variant on protein structure/function. Considering available information, this variant is classified as a variant of uncertain significance for Blau syndrome. References: Link to Infevers database: https://infevers.umai-montpellier.fr/web/search.php?n=6 Chamaillard M et al. Gene-environment interaction modulated by allelic heterogeneity in inflammatory diseases. Proc Natl Acad Sci U S A. 2003 Mar 18;100(6):3455-60. Huang H et al. Fine-mapping inflammatory bowel disease loci to single-variant resolution. Nature. 2017 Jul 13;547(7662):173-178. 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. Rivas MA et al. Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease. Nat Genet. 2011 Oct 9;43(11):1066-73.
Illumina Clinical Services Laboratory,Illumina RCV000084108 SCV001278496 benign Blau syndrome 2018-03-06 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Unité médicale des maladies autoinflammatoires, CHRU Montpellier RCV000084108 SCV000116239 not provided Blau syndrome no assertion provided not provided

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.