ClinVar Miner

Submissions for variant NM_014244.5(ADAMTS2):c.547C>T (p.Arg183Trp)

gnomAD frequency: 0.00005  dbSNP: rs372225444
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000523703 SCV000621019 uncertain significance not provided 2018-03-05 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the ADAMTS2 gene. The R183W variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The R183W variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, this substitution occurs at a position where amino acids with similar properties to arginine (R) are tolerated across species.
Invitae RCV000686820 SCV000814356 uncertain significance Ehlers-Danlos syndrome, dermatosparaxis type 2022-06-27 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 183 of the ADAMTS2 protein (p.Arg183Trp). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 452231). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Mayo Clinic Laboratories, Mayo Clinic RCV000523703 SCV001714757 uncertain significance not provided 2020-08-05 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000686820 SCV002814833 uncertain significance Ehlers-Danlos syndrome, dermatosparaxis type 2022-04-25 criteria provided, single submitter clinical testing
Natera, Inc. RCV000686820 SCV001462999 uncertain significance Ehlers-Danlos syndrome, dermatosparaxis type 2020-03-17 no assertion criteria provided clinical testing

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