ClinVar Miner

Submissions for variant NM_014244.5(ADAMTS2):c.2272G>A (p.Ala758Thr)

gnomAD frequency: 0.00054  dbSNP: rs146222244
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000762249 SCV000619588 uncertain significance not provided 2022-09-26 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Invitae RCV000646241 SCV000768004 uncertain significance Ehlers-Danlos syndrome, dermatosparaxis type 2022-09-07 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 758 of the ADAMTS2 protein (p.Ala758Thr). This variant is present in population databases (rs146222244, gnomAD 0.06%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with ADAMTS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 450954). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
CeGaT Center for Human Genetics Tuebingen RCV000762249 SCV000892537 uncertain significance not provided 2018-05-01 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000646241 SCV002816395 uncertain significance Ehlers-Danlos syndrome, dermatosparaxis type 2021-12-02 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000762249 SCV004227168 uncertain significance not provided 2023-04-05 criteria provided, single submitter clinical testing BP4
Natera, Inc. RCV000646241 SCV001458858 likely benign Ehlers-Danlos syndrome, dermatosparaxis type 2020-05-01 no assertion criteria provided clinical testing

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