Submissions for variant NM_014244.5(ADAMTS2):c.1194C>T (p.Asp398=)

gnomAD frequency: 0.20236  dbSNP: rs2278221

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000265344	SCV000342085	benign	not specified	2016-05-27	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000400563	SCV000456871	benign	Ehlers-Danlos syndrome, dermatosparaxis type	2018-01-12	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	RCV000265344	SCV000520272	benign	not specified	2016-10-06	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	RCV000588406	SCV000699360	benign	not provided	2016-11-25	criteria provided, single submitter	clinical testing	Variant summary: The c.1194C>T (p.Asp398=) in ADAMTS2 gene is a synonymous change that involves a non-conserved nucleotide. 4/5 programs in Alamut predict that this variant does not affect normal splicing, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in the control population dataset of ExAC at frequency of 0.267 (30190/113050 chrs tested), including 4040 homozygotes. The observed frequency exceeds the maximum expected allele frequency for a pathogenic variant in this gene (0.0029), suggesting that it is a benign polymorphism. The variant of interest has been cited as Benign by a reputable database/clinical laboratory. Taking together, based on the prevalence in general population the variant was classified as Benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000400563	SCV001730531	benign	Ehlers-Danlos syndrome, dermatosparaxis type	2025-02-04	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000400563	SCV001762708	benign	Ehlers-Danlos syndrome, dermatosparaxis type	2021-07-10	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000400563	SCV000734399	benign	Ehlers-Danlos syndrome, dermatosparaxis type		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000400563	SCV000745663	benign	Ehlers-Danlos syndrome, dermatosparaxis type	2014-11-19	no assertion criteria provided	clinical testing
Natera, Inc.	RCV000400563	SCV001457891	benign	Ehlers-Danlos syndrome, dermatosparaxis type	2020-09-16	no assertion criteria provided	clinical testing