Submissions for variant NM_014244.5(ADAMTS2):c.786G>A (p.Ala262=)

gnomAD frequency: 0.93088  dbSNP: rs423552

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000330251	SCV000456878	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	RCV000435641	SCV000520269	benign	not specified	2016-09-29	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	RCV000589419	SCV000699366	benign	not provided	2016-11-25	criteria provided, single submitter	clinical testing	Variant summary: The ADAMTS2 c.786G>A (p.Ala262Ala) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a polymorphism outcome for this variant. 4/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect multiple ESE sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 112782/121320 control chromosomes (52500 homozygotes) at a frequency of 0.9296241, which is approximately 322 times the estimated maximal expected allele frequency of a pathogenic ADAMTS2 variant (0.0028868), suggesting this variant is likely a benign polymorphism. Taken together, this variant is classified as benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000330251	SCV001725627	benign	Ehlers-Danlos syndrome, dermatosparaxis type	2025-02-04	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000330251	SCV001762777	benign	Ehlers-Danlos syndrome, dermatosparaxis type	2021-07-10	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000330251	SCV000734400	benign	Ehlers-Danlos syndrome, dermatosparaxis type		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000330251	SCV000745664	benign	Ehlers-Danlos syndrome, dermatosparaxis type	2014-11-19	no assertion criteria provided	clinical testing
Natera, Inc.	RCV000330251	SCV001458929	benign	Ehlers-Danlos syndrome, dermatosparaxis type	2020-09-16	no assertion criteria provided	clinical testing