ClinVar Miner

Submissions for variant NM_001370466.1(NOD2):c.2183C>T (p.Ala728Val) (rs61747625)

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 RCV000284123 SCV000397264 likely benign Inflammatory bowel disease 1 2017-04-27 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.
Illumina Clinical Services Laboratory,Illumina RCV000341511 SCV000397265 likely benign Blau syndrome 2017-04-27 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.
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000513725 SCV000609697 likely benign not provided 2017-06-14 criteria provided, single submitter clinical testing
Invitae RCV001086368 SCV000636100 likely benign Blau syndrome; Inflammatory bowel disease 1 2020-11-24 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001287091 SCV001473737 uncertain significance none provided 2019-10-25 criteria provided, single submitter clinical testing The NOD2 c.2264C>T; p.Ala755Val variant (rs61747625) is reported in the literature in one individual with a periodic fever syndrome and in several individuals with Crohn's disease or ulcerative colitis (Burillo-Sanz 2017, Hugot 2001, Lesage 2002, Rose 2015). The variant is also listed in the ClinVar database (Variation ID: 319462) and in the European (non-Finnish) population with an allele frequency of 0.4% (579/128986 alleles including 1 homozygote) in the Genome Aggregation Database. The alanine at codon 755 is highly conserved and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Although this variant has a population frequency incompatible with a periodic fever disease such as Blau syndrome, given the lack of clinical and functional data, the significance of the p.Ala755Val variant is uncertain at this time. References: Burillo-Sanz et al. Mutational profile of rare variants in inflammasome-related genes in Behcet disease: A Next Generation Sequencing approach. Sci Rep. 2017 Aug 16;7(1):8453. Hugot et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature. 2001 May 31;411(6837):599-603. 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. Rose et al. Blau syndrome: cross-sectional data from a multicentre study of clinical, radiological and functional outcomes. Rheumatology (Oxford). 2015 Jun;54(6):1008-16.
GeneDx RCV000513725 SCV001788319 uncertain significance not provided 2020-10-22 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 32222431, 28422189, 31760574, 28887115, 22056582, 12115249, 18640012, 16965521, 11875755, 20032092, 16485124, 28814775, 25416713, 11385576)

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.