Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
ARUP Laboratories, |
RCV000757206 | SCV000885350 | pathogenic | not provided | 2018-06-07 | criteria provided, single submitter | clinical testing | The EDA c.252delT; p.Gly85fs variant, also known as 494delT, is reported in the medical literature in individuals with X-linked anhidrotic ectodermal dysplasia (He 2013, Kere 1996). This variant is absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. This variant causes a frameshift by deleting a single nucleotide, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. References: He H et al. Involvement of and interaction between WNT10A and EDA mutations in tooth agenesis cases in the Chinese population. PLoS One. 2013 Nov 27;8(11):e80393. Kere J et al. X-linked anhidrotic (hypohidrotic) ectodermal dysplasia is caused by mutation in a novel transmembrane protein. Nat Genet. 1996 Aug;13(4):409-16. |
Invitae | RCV000821716 | SCV000962485 | pathogenic | Hypohidrotic X-linked ectodermal dysplasia | 2018-12-28 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in EDA are known to be pathogenic (PMID: 9683615). This variant has been observed in several individuals affected with hypohidrotic ectodermal dysplasia (HED) (PMID: 8696334, 27305980, Invitae) as well as in an individual with syndromic tooth agenesis including anhidrosis (PMID: 24312213). In addition, this variant was observed to segregate with HED in a family (PMID: 8696334). This variant is also known as c.494delT in the literature. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gly85Alafs*6) in the EDA gene. It is expected to result in an absent or disrupted protein product. |
Genetics and Molecular Pathology, |
RCV002466577 | SCV002761544 | pathogenic | Tooth agenesis, selective, X-linked, 1 | 2022-05-17 | criteria provided, single submitter | clinical testing |