ClinVar Miner

Submissions for variant NM_014244.5(ADAMTS2):c.1993G>A (p.Gly665Arg)

gnomAD frequency: 0.00904  dbSNP: rs35372714
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000514314 SCV000525845 benign not provided 2018-04-26 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 27377421)
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics RCV000514314 SCV000610815 likely benign not provided 2017-05-30 criteria provided, single submitter clinical testing
Invitae RCV001082472 SCV000647114 benign Ehlers-Danlos syndrome, dermatosparaxis type 2024-02-01 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000435060 SCV000916423 benign not specified 2021-01-11 criteria provided, single submitter clinical testing Variant summary: ADAMTS2 c.1993G>A (p.Gly665Arg) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0078 in 251246 control chromosomes in the gnomAD database, including 21 homozygotes. The observed variant frequency is approximately 3 fold of 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.1993G>A in individuals affected with Ehlers-Danlos Syndrome, Type VIIC (Dermatosparaxis) and no experimental evidence demonstrating its impact on protein function have been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Illumina Laboratory Services, Illumina RCV001082472 SCV001315710 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.
CeGaT Center for Human Genetics Tuebingen RCV000514314 SCV002497375 benign not provided 2023-07-01 criteria provided, single submitter clinical testing ADAMTS2: BS1, BS2
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV002279184 SCV002565534 benign Ehlers-Danlos syndrome 2022-04-28 criteria provided, single submitter clinical testing
Natera, Inc. RCV001082472 SCV002081941 benign Ehlers-Danlos syndrome, dermatosparaxis type 2019-12-09 no assertion criteria provided clinical testing

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