Submissions for variant NM_022336.4(EDAR):c.1121G>A (p.Trp374Ter)

dbSNP: rs886039348

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000256050	SCV000321590	likely pathogenic	not provided	2021-10-14	criteria provided, single submitter	clinical testing	Nonsense variant in the C-terminus predicted to result in protein truncation, as the last 75 amino acids are lost, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (Stenson et al., 2014); Not observed at significant frequency in large population cohorts (Lek et al., 2016); Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp	RCV001068701	SCV001233828	pathogenic	Ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant; Autosomal recessive hypohidrotic ectodermal dysplasia syndrome	2025-01-27	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Trp374*) in the EDAR gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 75 amino acid(s) of the EDAR protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with EDAR-related conditions (internal data). ClinVar contains an entry for this variant (Variation ID: 265115). This variant disrupts a region of the EDAR protein in which other variant(s) (p.Phe398*) have been determined to be pathogenic (PMID: 23401279, 24641098). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.