Submissions for variant NM_001399.5(EDA):c.612_629del (p.202_204IPG[1])

dbSNP: rs1064793104

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000487168	SCV000564954	likely pathogenic	not provided	2025-03-19	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on protein structure/function; In-frame deletion of 6 amino acid(s) in a non-repeat region; This variant is associated with the following publications: (PMID: 23991204, 31796081)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000805136	SCV000945081	pathogenic	Hypohidrotic X-linked ectodermal dysplasia	2024-05-12	criteria provided, single submitter	clinical testing	This variant, c.612_629del, results in the deletion of 6 amino acid(s) of the EDA protein (p.Ile205_Gly210del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (no rsID available, gnomAD 0.005%). This variant has been observed in individual(s) with clinical features of ectodermal dysplasia and non-syndromic tooth agenesis (PMID: 23991204; Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 418170). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant disrupts the p.Pro206 amino acid residue in EDA. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Molecular Diagnostics Laboratory, M Health Fairview: University of Minnesota	RCV000805136	SCV001142706	likely pathogenic	Hypohidrotic X-linked ectodermal dysplasia	2019-05-16	criteria provided, single submitter	clinical testing
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV004787773	SCV005398372	likely pathogenic	Tooth agenesis, selective, X-linked, 1	2024-10-09	criteria provided, single submitter	clinical testing	Based on the classification scheme VCGS_Germline_v1.3.5, this variant is classified as Likely pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with X-linked recessive ectodermal dysplasia 1, hypohidrotic (HED; MIM#305100) and X-linked dominant tooth agenesis, selective 1 (TA; MIM#313500). (I) 0108 - This gene is associated with both X-linked recessive and dominant disease. Female carriers of variants causing either condition may be normal or mildly affected, depending on skewed X-inactivation (PMID: 18510547, 16583127). (I) 0214 - In-frame deletion fully contained in a repetitive region that has high conservation. (SP) 0253 - This variant is hemizygous. (I) 0304 - Variant is present in gnomAD (v4) <0.0 (1 heterozygote, 0 homozygotes, 0 hemizygotes). (SP) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (I) 0705 - No comparable in-frame deletion variants have previous evidence for pathogenicity. (I) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been classified as likely pathogenic and pathogenic by clinical laboratories in ClinVar. This variant has also been observed in two unrelated hemizygous males with EDA-related symptoms, and was confirmed de novo in one (PMID: 31796081, 23991204). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1205 - This variant has been shown to be maternally inherited (by trio analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign