ClinVar Miner

Submissions for variant NM_000393.5(COL5A2):c.4067A>G (p.Asp1356Gly) (rs140952583)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000196787 SCV000249988 uncertain significance not provided 2018-10-26 criteria provided, single submitter clinical testing The D1356G variant of uncertain significance in the COL5A2 gene has not been published as pathogenic or benign to our knowledge. The D1356G variant is observed in 28/34,410 (0.08%) alleles from individuals of Latino background and 69/126,486 (0.05%) alleles from individuals of European (non-Finnish) background in large population cohorts (Lek et al., 2016). In addition, although D1356G has been identified both independently and in conjunction with additional cardiogenetic variants in individuals referred for connective tissue disorder testing at GeneDx, limited segregation data from two relatives with signs/symptoms of EDS suggests lack of variant segregation with disease in the family. Furthermore, D1356G is not located in the triple helical region, where the majority of pathogenic missense variants occur (Symoens et al., 2012; Stenson et al., 2014). Nevertheless, D1356G 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. Moreover, in-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign.
Illumina Clinical Services Laboratory,Illumina RCV000299510 SCV000425614 likely benign Ehlers-Danlos syndrome, type 7A 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV001079206 SCV000547866 likely benign Ehlers-Danlos syndrome, classic type 2019-12-31 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001139303 SCV001299435 likely benign Ehlers-Danlos syndrome classic type 2 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.

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.