Submissions for variant NM_001399.5(EDA):c.526+5G>T

dbSNP: rs397516664

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000037174	SCV000060831	likely pathogenic	Hypohidrotic X-linked ectodermal dysplasia	2015-01-26	criteria provided, single submitter	clinical testing	The c.526+5G>T variant in EDA has not been reported in the literature but has be en identified in 2 individuals from the same family with X-linked hypohidrotic e ctodermal dysplasia (XLHED) by our laboratory (1 adult female and 1 male). This variant is located in the 5' splice region. Computational tools do suggest an im pact to splicing. However, this information is not predictive enough to determin e pathogenicity. In summary, although additional studies are required to fully e stablish its clinical significance, the c.526+5G>T variant is likely pathogenic based upon the predicted splice impact and its presence it two affected individu als.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000037174	SCV005748049	likely pathogenic	Hypohidrotic X-linked ectodermal dysplasia	2024-06-12	criteria provided, single submitter	clinical testing	This sequence change falls in intron 3 of the EDA gene. It does not directly change the encoded amino acid sequence of the EDA protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with hypohidrotic ectodermal dysplasia (PMID: 26345974; Invitae). ClinVar contains an entry for this variant (Variation ID: 44196). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant disrupts the c.526G nucleotide in the EDA gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (Invitae). This suggests that this nucleotide is clinically significant, and that variants that disrupt this position are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.