ClinVar Miner

Submissions for variant NM_000393.5(COL5A2):c.5T>C (p.Met2Thr) (rs762874073)

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
Ambry Genetics RCV000251652 SCV000320325 uncertain significance Cardiovascular phenotype 2017-12-04 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
GeneDx RCV000200003 SCV000250001 uncertain significance not provided 2018-03-13 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the COL5A2 gene. The M2T variant has not been published as pathogenic or been reported as benign to our knowledge. This variant has been identified independently and/or in conjunction with additional cardiogenetic variants in individuals referred for genetic testing at GeneDx. So far, segregation data is limited or absent for these individuals due to the lack of clinical information provided and/or insufficient participation by informative family members. The M2T variant is observed in 8/101052 (0.01%) alleles from individuals of European (non-Finnish) ancestry in large population cohorts (Lek et al., 2016). The M2T 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. However, in-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function.
Invitae RCV000557923 SCV000631612 uncertain significance Ehlers-Danlos syndrome, classic type 2018-07-03 criteria provided, single submitter clinical testing This sequence change replaces methionine with threonine at codon 2 of the COL5A2 protein (p.Met2Thr). The methionine residue is moderately conserved and there is a moderate physicochemical difference between methionine and threonine. This variant is present in population databases (rs762874073, ExAC 0.008%). This variant has not been reported in the literature in individuals with a COL5A2-related disease. ClinVar contains an entry for this variant (Variation ID: 213138). 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, this variant has uncertain impact on COL5A2 function. The available evidence is currently insufficient to determine its role 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.