ClinVar Miner

Submissions for variant NM_014244.5(ADAMTS2):c.547C>T (p.Arg183Trp) (rs372225444)

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Total submissions: 2
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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, type vii, autosomal recessive 2018-05-21 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 183 of the ADAMTS2 protein (p.Arg183Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs372225444, ExAC 0.002%). This variant has not been reported in the literature in individuals with ADAMTS2-related disease. ClinVar contains an entry for this variant (Variation ID: 452231). Algorithms developed to predict the effect of missense changes on protein structure and function 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.

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