Submissions for variant NM_001399.5(EDA):c.572_589del (p.188_190PGP[1])

dbSNP: rs397516668

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000633503	SCV000060835	pathogenic	Hypohidrotic X-linked ectodermal dysplasia	2012-04-10	criteria provided, single submitter	clinical testing	The Pro191_Pro196del (EDA) has not been reported in one individual with X-linked anhidrotic ectodermal dysplasia (Bayes 1998). This variant results in an in-fra me deletion of 6 amino acids from the conserved Gly-X-Y repeats of the collagen subdomain of the EDA protein. Several adjacent and overlapping in-frame deletion s have been identified in patients with clinical features of X-linked hypohidrot ic ectodermal dysplasia (Bayes 1998, Cluzeau 2011, LMM unpublished data). In sum mary, this variant meets our criteria to be classified as pathogenic.
GeneDx	RCV000481357	SCV000566561	pathogenic	not provided	2021-01-25	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; In-frame deletion of 6 amino acids in a non-repeat region; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 26345974, 20979233, 11279189, 31924237, 31796081, 30394555, 27305980, 9736768)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000633503	SCV000754739	pathogenic	Hypohidrotic X-linked ectodermal dysplasia	2024-01-29	criteria provided, single submitter	clinical testing	This variant, c.572_589del, results in the deletion of 6 amino acid(s) of the EDA protein (p.Pro191_Pro196del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with hypohidrotic ectodermal dysplasia (PMID: 9736768, 11279189, 27305980). In at least one individual the variant was observed to be de novo. This variant is also known as 801/814del18. ClinVar contains an entry for this variant (Variation ID: 44200). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. For these reasons, this variant has been classified as Pathogenic.
CeGaT Center for Human Genetics Tuebingen	RCV000481357	SCV001746145	pathogenic	not provided	2021-05-01	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000633503	SCV002103648	pathogenic	Hypohidrotic X-linked ectodermal dysplasia	2022-02-08	criteria provided, single submitter	clinical testing	Variant summary: EDA c.572_589del18 (p.Pro191_Pro196del) results in an in-frame deletion that is predicted to remove 6 amino acids from the encoded protein. The variant was absent in 126835 control chromosomes (gnomAD). c.572_589del18 has been reported in the literature in multiple individuals/families affected with Hypohidrotic X-Linked Ectodermal Dysplasia (e.g. Bayes_1998, Schneider_2001, Martinez-Romero_2019, Wohlfart_2020). These data indicate that the variant is very likely to be associated with disease. Three ClinVar submitters (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Institute of Human Genetics, University of Leipzig Medical Center	RCV000633503	SCV004242417	pathogenic	Hypohidrotic X-linked ectodermal dysplasia	2024-01-08	criteria provided, single submitter	clinical testing	Criteria applied: PS4,PM1,PM4,PS2_SUP,PM2_SUP
PreventionGenetics, part of Exact Sciences	RCV003904911	SCV004723776	pathogenic	EDA-related disorder	2024-01-26	criteria provided, single submitter	clinical testing	The EDA c.572_589del18 variant is predicted to result in an in-frame deletion (p.Pro191_Pro196del). This variant is also a deletion in the collagen triple helix repeat domain of the EDA protein. This variant has been reported in patients affected with ectodermal dysplasia (Bayés et al. 1998. PubMed ID: 9736768; Wohlfart et al. 2016. PubMed ID: 27305980). Several similar deletions have also been reported to be pathogenic (Cluzeau et al. 2011. PubMed: 20979233; Schneider et al. 2011. PubMed: 21357618). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is interpreted as pathogenic.
Natera, Inc.	RCV000633503	SCV002087202	pathogenic	Hypohidrotic X-linked ectodermal dysplasia	2020-10-21	no assertion criteria provided	clinical testing
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV000633503	SCV004806459	uncertain significance	Hypohidrotic X-linked ectodermal dysplasia	2024-03-25	flagged submission	clinical testing