Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002514490 | SCV000759554 | benign | Blau syndrome; Regional enteritis | 2024-01-04 | criteria provided, single submitter | clinical testing | |
ARUP Laboratories, |
RCV001811399 | SCV001474128 | uncertain significance | not provided | 2020-03-06 | criteria provided, single submitter | clinical testing | The NOD2 c.743T>G; p.Leu248Arg variant (rs104895423) is reported in one individual with diagnoses of Behcet and Crohn's disease (Burillo-Sanz 2017) and in several individuals with Crohn's disease or inflammatory bowel disease (Girardelli 2018, Lesage 2002, Rivas 2018, Schiff 2018). The variant is reported in the general population with an overall allele frequency of 0.05% (147/282,764 alleles including 2 homozygotes) in the Genome Aggregation Database and is listed in the ClinVar database (Variation ID: 97881). The leucine at codon 248 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Additionally, functional studies show this variant protein does not associate with the membrane or respond to signals as the wild type protein (Parkhouse and Monie 2015). This variant may be a risk factor for Crohn's disease, possibly contributing together with other genetic and/or environmental factors. However, the significance of this variant specifically associated with a periodic fever disease such as Blau syndrome remains uncertain. References: Burillo-Sanz S 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. Girardelli M et al. Genetic profile of patients with early onset inflammatory bowel disease. Gene. 2018 Mar 1;645:18-29. 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. Parkhouse R and Monie TP. Dysfunctional Crohn's Disease-Associated NOD2 Polymorphisms Cannot be Reliably Predicted on the Basis of RIPK2 Binding or Membrane Association. Front Immunol. 2015 Oct 8;6:521. Rivas MA et al. Insights into the genetic epidemiology of Crohn's and rare diseases in the Ashkenazi Jewish population. PLoS Genet. 2018 May 24;14(5):e1007329. Schiff ER et al. Rare coding variant analysis in a large cohort of Ashkenazi Jewish families with inflammatory bowel disease. Hum Genet. 2018 Sep;137(9):723-734. |
Baylor Genetics | RCV000084138 | SCV001526896 | uncertain significance | Blau syndrome | 2018-05-30 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |
Genome Diagnostics Laboratory, |
RCV002260989 | SCV002542746 | likely benign | Autoinflammatory syndrome | 2019-12-01 | criteria provided, single submitter | clinical testing | |
Unité médicale des maladies autoinflammatoires, |
RCV000084138 | SCV000116269 | not provided | Blau syndrome | no assertion provided | not provided |