Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000689256 | SCV000816898 | pathogenic | Hypohidrotic X-linked ectodermal dysplasia | 2020-09-04 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in EDA are known to be pathogenic (PMID: 9683615). A different variant affecting this nucleotide (c.527-2A>C) has been reported in multiple individuals affected with ectodermal dysplasia (PMID: 24724966). This suggests that this nucleotide is important for normal RNA splicing, and that other variants at this position may also be pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with EDA-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 3 of the EDA gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. |