Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Al Jalila Children's Genomics Center, |
RCV001269323 | SCV001448259 | pathogenic | Familial cold autoinflammatory syndrome 2 | 2020-10-04 | criteria provided, single submitter | clinical testing | |
| ARUP Laboratories, |
RCV001269323 | SCV002050258 | uncertain significance | Familial cold autoinflammatory syndrome 2 | 2020-12-16 | criteria provided, single submitter | clinical testing | The NLRP12 c.1952C>A; p.Ser651Ter variant (rs781361326), to our knowledge, is not reported in the medical literature or gene-specific databases. This variant is found on only four chromosomes (4/251382 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. While loss-of-function variants in NLRP12 have been reported in individuals affected with autoinflammatory disease or periodic fever syndromes (Hua 2019, Jeru 2008, Kostik 2018, Xia 2016), the mechanism by which such variants cause disease remains uncertain (Tuncer 2014). Due to limited information, the clinical significance of the p.Ser651Ter variant is uncertain at this time. References: Hua Y et al. Phenotypes and genotypes of Chinese adult patients with systemic autoinflammatory diseases. Semin Arthritis Rheum. 2019 Dec;49(3):446-452. Jeru I et al. Mutations in NALP12 cause hereditary periodic fever syndromes. Proc Natl Acad Sci U S A. 2008 Feb 5;105(5):1614-9. Kostik MM et al. Multigene sequencing reveals heterogeneity of NLRP12-related autoinflammatory disorders. Rheumatol Int. 2018 May;38(5):887-893. Tuncer S et al. The multifaceted nature of NLRP12. J Leukoc Biol. 2014 Dec;96(6):991-1000. Xia X et al. Identification of a Novel NLRP12 Nonsense Mutation (Trp408X) in the Extremely Rare Disease FCAS by Exome Sequencing. PLoS One. 2016 Jun 17;11(6):e0156981. |