Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002553764 | SCV001218200 | uncertain significance | Blau syndrome; Regional enteritis | 2023-08-22 | criteria provided, single submitter | clinical testing | 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. ClinVar contains an entry for this variant (Variation ID: 849868). This premature translational stop signal has been observed in individual(s) with clinical features of infammatory bowel disease (PMID: 33692434). This variant is present in population databases (rs781333877, gnomAD 0.01%). This sequence change creates a premature translational stop signal (p.Gln233*) in the NOD2 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in NOD2 cause disease. |
| Laboratory for Molecular Medicine, |
RCV001195504 | SCV001365882 | uncertain significance | not specified | 2019-08-02 | criteria provided, single submitter | clinical testing | The p.Gln233X variant in NOD2 has not been previously reported in individuals with Blau syndrome or Crohn's disease but has been identified in 0.01% (4/34590) of Latino chromosomes by gnomAD (http://gnomad.broadinstitute.org). This nonsense variant leads to a premature termination codon at position 233, which is predicted to lead to a truncated or absent protein. Loss of function of NOD2 is not an established mechanism for disease. In summary, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: None applied. |
| ARUP Laboratories, |
RCV001811632 | SCV001471848 | uncertain significance | not provided | 2020-03-12 | criteria provided, single submitter | clinical testing | The NOD2 c.697C>T; p.Gln233Ter variant (rs781333877), to our knowledge, is not reported in the medical literature but is listed in a gene specific database in one individual affected with Blau syndrome and in an unaffected parent (see link below). The variant is reported in the general population with an overall allele frequency of 0.003% (8/251,468 alleles) in the Genome Aggregation Database. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Loss-of-function variants are not an established mechanism of disease for Blau syndrome, but have been associated with an increased risk for Crohn's disease (Huang 2017). Thus, due to limited information, the clinical significance of the p.Gln233Ter variant is uncertain at this time. REFERENCES: Link to Infevers database: https://infevers.umai-montpellier.fr/web/search.php?n=6 Huang H et al. Fine-mapping inflammatory bowel disease loci to single-variant resolution. Nature. 2017 Jul 13;547(7662):173-178. |