Submissions for variant NM_022336.4(EDAR):c.68C>T (p.Ser23Leu)

gnomAD frequency: 0.00014  dbSNP: rs760731007

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000337432	SCV000415854	uncertain significance	Hypohidrotic Ectodermal Dysplasia, Dominant	2016-06-14	criteria provided, single submitter	clinical testing
Invitae	RCV002229875	SCV000760959	uncertain significance	Ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant; Autosomal recessive hypohidrotic ectodermal dysplasia syndrome	2023-01-28	criteria provided, single submitter	clinical testing	In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt EDAR protein function. ClinVar contains an entry for this variant (Variation ID: 330712). This missense change has been observed in individual(s) with clinical features of EDAR-related conditions (Invitae). This variant is present in population databases (rs760731007, gnomAD 0.1%). This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 23 of the EDAR protein (p.Ser23Leu).
Illumina Laboratory Services, Illumina	RCV001135565	SCV001295353	likely benign	Hypohidrotic ectodermal dysplasia	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Ambry Genetics	RCV002521263	SCV003567978	uncertain significance	Inborn genetic diseases	2022-07-27	criteria provided, single submitter	clinical testing	The c.68C>T (p.S23L) alteration is located in exon 3 (coding exon 2) of the EDAR gene. This alteration results from a C to T substitution at nucleotide position 68, causing the serine (S) at amino acid position 23 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences	RCV003950136	SCV004775801	uncertain significance	EDAR-related disorder	2024-01-22	criteria provided, single submitter	clinical testing	The EDAR c.68C>T variant is predicted to result in the amino acid substitution p.Ser23Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.11% of alleles in individuals of Latino descent in gnomAD. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.