ClinVar Miner

Submissions for variant NM_014244.5(ADAMTS2):c.847G>A (p.Gly283Arg) (rs376856341)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000497894 SCV000590196 uncertain significance not provided 2017-06-06 criteria provided, single submitter clinical testing The G283R variant in the ADAMTS2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This variant is observed in 9/66378 (0.014%) alleles from individuals of non-Finnish European background in the ExAC dataset (Lek et al., 2016). The G283R 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. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret G283R as a variant of uncertain significance.
Invitae RCV000795669 SCV000935138 uncertain significance Ehlers-Danlos syndrome dermatosparaxis type 2018-12-18 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 283 of the ADAMTS2 protein (p.Gly283Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs376856341, ExAC 0.01%). This variant has not been reported in the literature in individuals with ADAMTS2-related disease. ClinVar contains an entry for this variant (Variation ID: 432468). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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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