Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000156051 | SCV000205764 | uncertain significance | not specified | 2013-10-31 | criteria provided, single submitter | clinical testing | The Asp265Gly variant in EDA has not been previously reported in individuals wit h ectodermal dysplasia or in large population studies. A different amino acid ch ange at this position (Arg265Asn) has been seen in one individual with clinical features of ectodermal dysplasia by our laboratory, but it is unclear if that va riant was the cause of the clinical features. The aspartic acid (Asp) residue at position 265 is highly conserved across mammals and evolutionarily distant spec ies, suggesting that a change to the amino acid may not be tolerated. In additio n, computational analyses (biochemical amino acid properties, AlignGVGD, PolyPhe n2, and SIFT) suggest that the Asp265Gly variant may impact the protein. Alterna tively, although this variant is located in the first base of the exon, which is part of the 5? splice consensus region, computational tools do not predict alte red splicing. However, the accuracy of these predicative tools is unknown and th erefore, not predictive enough to assume or rule out pathogenicity. In summary, additional information is needed to fully assess the clinical significance of th e Asp265Gly variant. |
| ARUP Laboratories, |
RCV000156051 | SCV000603412 | likely pathogenic | not specified | 2016-09-07 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000796602 | SCV000936122 | pathogenic | Hypohidrotic X-linked ectodermal dysplasia | 2023-03-30 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 179264). This missense change has been observed in individual(s) with hypohidrotic ectodermal dysplasia (PMID: 25333067; Invitae). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 265 of the EDA protein (p.Asp265Gly). |
| Institute of Human Genetics, |
RCV000796602 | SCV002102450 | uncertain significance | Hypohidrotic X-linked ectodermal dysplasia | 2022-02-17 | criteria provided, single submitter | clinical testing | This variant was identified as hemizygous. Variant was inherited from mildly affected mother (one tooth is missing). Criteria applied: PS4_MOD, PM2_SUP, PP1, PP3 |