Submissions for variant NM_014244.5(ADAMTS2):c.2532C>T (p.Asp844=)

gnomAD frequency: 0.17766  dbSNP: rs2303644

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000399683	SCV000456848	benign	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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
GeneDx	RCV000430441	SCV000520277	benign	not specified	2016-09-30	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000430441	SCV000916420	benign	not specified	2018-07-05	criteria provided, single submitter	clinical testing	Variant summary: ADAMTS2 c.2532C>T results in a synonymous change. The variant allele was found at a frequency of 0.2 in 121298 control chromosomes in the ExAC database, including 2859 homozygotes. The observed variant frequency is approximately 70 fold above the estimated maximal expected allele frequency for a pathogenic variant in ADAMTS2 causing Ehlers-Danlos Syndrome, Type VIIC (Dermatosparaxis) phenotype (0.0029), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.2532C>T in individuals affected with Ehlers-Danlos Syndrome, Type VIIC (Dermatosparaxis) and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and both classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
Genome-Nilou Lab	RCV000399683	SCV001623493	benign	Ehlers-Danlos syndrome, dermatosparaxis type	2021-05-18	criteria provided, single submitter	clinical testing
Invitae	RCV000399683	SCV001730538	benign	Ehlers-Danlos syndrome, dermatosparaxis type	2024-02-01	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000399683	SCV001457875	benign	Ehlers-Danlos syndrome, dermatosparaxis type	2020-09-16	no assertion criteria provided	clinical testing