ClinVar Miner

Submissions for variant NM_014244.5(ADAMTS2):c.1883G>A (p.Arg628His) (rs140621260)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000431482 SCV000531939 uncertain significance not specified 2017-08-17 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the ADAMTS2 gene. The R628H variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is observed in 94/87886 (0.1%) alleles from individuals of European (non-Finnish) background, in 11/24106 (0.05%) alleles from individuals of South Asian background and in 11/18124 (0.06%) alleles from individuals of African ancestry in large population cohorts (Lek et al., 2016). The R628H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Although this substitution occurs at a position that is conserved in mammals, in silico predicts this variant likely does not alter the protein structure/function.
Illumina Clinical Services Laboratory,Illumina RCV000331977 SCV000456864 uncertain significance Ehlers-Danlos syndrome, type vii, autosomal recessive 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000331977 SCV000647111 uncertain significance Ehlers-Danlos syndrome, type vii, autosomal recessive 2018-12-07 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 628 of the ADAMTS2 protein (p.Arg628His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs140621260, ExAC 0.2%), including one homozygous individual. This variant has not been reported in the literature in individuals with ADAMTS2-related disease. ClinVar contains an entry for this variant (Variation ID: 353118). 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: "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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.