ClinVar Miner

Submissions for variant NM_000089.4(COL1A2):c.432+1G>A

dbSNP: rs1554395431
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 RCV000521677 SCV000618350 likely pathogenic not provided 2017-03-21 criteria provided, single submitter clinical testing The c.432+1 G>A likely pathogenic variant in the COL1A2 gene has not been reported as pathogenic or benign to our knowledge. This variant destroys the canonical splice donor site of intron nine and is predicted to cause skipping of exon nine, although it does not result in a shift in reading frame or a premature stop codon. Many other canonical splice site variants in the COL1A2 gene have been reported in HGMD (Stenson et al., 2014). Furthermore, c.432+1 G>A is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server).
Ambry Genetics RCV000624372 SCV000741973 pathogenic Inborn genetic diseases 2016-12-03 criteria provided, single submitter clinical testing
Invitae RCV002231211 SCV000817187 pathogenic Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 2022-09-13 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 449890). Disruption of this splice site has been observed in individual(s) with clinical features of COL1A2-related conditions (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 9 of the COL1A2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in COL1A2 are known to be pathogenic (PMID: 11288717, 15077201).

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.