Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000497685 | SCV000590087 | uncertain significance | not provided | 2017-05-31 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the ADAMTS2 gene. The D606N 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; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The D606N variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. However, this substitution occurs at a position where amino acids with similar properties to aspartic acid are tolerated across species. In silico analysis suggests that this variant is probably damaging to the protein structure/function. |
Invitae | RCV001834607 | SCV002112154 | uncertain significance | Ehlers-Danlos syndrome, dermatosparaxis type | 2022-07-25 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 606 of the ADAMTS2 protein (p.Asp606Asn). This variant is present in population databases (rs138399615, gnomAD 0.1%). 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: 432369). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The asparagine 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. |
Natera, |
RCV001834607 | SCV002081946 | uncertain significance | Ehlers-Danlos syndrome, dermatosparaxis type | 2019-10-28 | no assertion criteria provided | clinical testing |