ClinVar Miner

Submissions for variant NM_000089.3(COL1A2):c.2827G>A (p.Gly943Arg) (rs193922165)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000622423 SCV000742730 uncertain significance Inborn genetic diseases 2017-08-24 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: POSITIVE: Relevant Alteration(s) Detected
Integrated Genetics/Laboratory Corporation of America RCV000029600 SCV000052252 likely pathogenic Osteogenesis imperfecta 2019-01-24 criteria provided, single submitter clinical testing Variant summary: COL1A2 c.2827G>A (p.Gly943Arg) results in a non-conservative amino acid change affecting a critical amino acid residue in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. Substitutions of glycine in COL1A2 by charged residues such as arginine have been reported as more likely to lead to a lethal outcome (Marini et al, 2007). The variant allele was found at a frequency of 8.2e-06 in 121362 control chromosomes. To our knowledge, no occurrence of c.2827G>A in individuals affected with Osteogenesis Imperfecta and no experimental evidence demonstrating its impact on protein function have been reported. However, a different amino acid substitution at the same codon, p.G943E has been listed in association with OI-III indicating the potential functional relevance of this residue in collagen assembly. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely pathogenic.

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.