Submissions for variant NM_014244.5(ADAMTS2):c.733G>A (p.Val245Ile)

gnomAD frequency: 0.32945  dbSNP: rs398829

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000384500	SCV000456882	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	RCV000425362	SCV000520268	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	RCV000589550	SCV000699363	benign	not provided	2016-11-25	criteria provided, single submitter	clinical testing	Variant summary: The ADAMTS2 c.733G>A (p.Val245Ile) variant involves the alteration of a non-conserved nucleotide. 5/5 in silico tools predict a benign outcome for this variant . This variant was found in 42957/120864 control chromosomes (8516 homozygotes) at a frequency of 0.355416, which is approximately 123 times the estimated maximal expected allele frequency of a pathogenic ADAMTS2 variant (0.0028868), suggesting this variant is likely a benign polymorphism. . The variant of interest has been cited as Polymorphism in published report(s). Taking together, based on the prevalence in general population the variant was classified as Benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000384500	SCV001725628	benign	Ehlers-Danlos syndrome, dermatosparaxis type	2025-02-04	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000384500	SCV001762778	benign	Ehlers-Danlos syndrome, dermatosparaxis type	2021-07-10	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000384500	SCV000734401	benign	Ehlers-Danlos syndrome, dermatosparaxis type		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000384500	SCV000745665	benign	Ehlers-Danlos syndrome, dermatosparaxis type	2014-02-04	no assertion criteria provided	clinical testing
Natera, Inc.	RCV000384500	SCV001458930	benign	Ehlers-Danlos syndrome, dermatosparaxis type	2020-09-16	no assertion criteria provided	clinical testing