ClinVar Miner

Submissions for variant NM_014244.5(ADAMTS2):c.655C>T (p.Pro219Ser)

gnomAD frequency: 0.00003  dbSNP: rs146217716
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000487339 SCV000568120 uncertain significance not provided 2017-03-01 criteria provided, single submitter clinical testing The P219S variant in the ADAMTS2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, in association with dermatosparaxis type EDS to our knowledge. The P219S variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The P219S 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 not conserved. In silico analysis predicts this variant likely does not alter the protein structure/function. We interpret P219S as a variant of uncertain significance.
Fulgent Genetics, Fulgent Genetics RCV000764596 SCV000895693 uncertain significance Ehlers-Danlos syndrome, dermatosparaxis type 2018-10-31 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000764596 SCV001205072 uncertain significance Ehlers-Danlos syndrome, dermatosparaxis type 2022-04-08 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 219 of the ADAMTS2 protein (p.Pro219Ser). This variant is present in population databases (rs146217716, gnomAD 0.007%). 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: 419919). 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: "Benign"; 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.
Natera, Inc. RCV000764596 SCV001458934 uncertain significance Ehlers-Danlos syndrome, dermatosparaxis type 2020-09-16 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004751558 SCV005345377 uncertain significance ADAMTS2-related disorder 2024-06-17 no assertion criteria provided clinical testing The ADAMTS2 c.655C>T variant is predicted to result in the amino acid substitution p.Pro219Ser. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.012% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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