Submissions for variant NM_014244.5(ADAMTS2):c.2439C>T (p.His813=)

gnomAD frequency: 0.00030  dbSNP: rs141661592

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000344325	SCV000456850	uncertain significance	Ehlers-Danlos syndrome, dermatosparaxis type	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae	RCV000344325	SCV000768007	benign	Ehlers-Danlos syndrome, dermatosparaxis type	2024-01-07	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001310890	SCV001500867	likely benign	not provided	2022-05-01	criteria provided, single submitter	clinical testing	ADAMTS2: BP4, BP7
GeneDx	RCV001310890	SCV001823033	likely benign	not provided	2019-04-22	criteria provided, single submitter	clinical testing	In silico analysis, which includes splice predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Nucleotide substitution has no predicted effect on splicing and is not conserved across species; Has not been previously published as pathogenic or benign to our knowledge
PreventionGenetics, part of Exact Sciences	RCV003957824	SCV004767921	likely benign	ADAMTS2-related condition	2023-12-15	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Natera, Inc.	RCV000344325	SCV001458855	likely benign	Ehlers-Danlos syndrome, dermatosparaxis type	2020-05-01	no assertion criteria provided	clinical testing