ClinVar Miner

Submissions for variant NM_000089.3(COL1A2):c.226-2A>G (rs72656355)

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 RCV000433468 SCV000520910 likely pathogenic not provided 2017-02-02 criteria provided, single submitter clinical testing The c.226-2A>G pathogenic variant in the COL1A2 gene has been reported in multiple affected individuals from a family segregating an autosomal dominant form of Ehlers-Danlos syndrome characterized by marked joint laxity and multiple dislocations, with no reported skin fragility or fractures (Byers et al., 1997). This splice site variant destroys the canonical splice acceptor site in intron 5. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. The c.226-2A>G variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.226-2A>G as a likely pathogenic variant
Invitae RCV000792672 SCV000931982 pathogenic Ehlers-Danlos syndrome, classic type; Osteogenesis imperfecta type I 2018-12-10 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 5 of the COL1A2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with Ehlers-Danlos syndrome in a family (PMID: 9295084) and has been observed in an unrelated individual with arthrochalasia type Ehlers-Danlos syndrome (PMID: 21801164). This variant is also known as Intron 5 A-2>G in the literature. ClinVar contains an entry for this variant (Variation ID: 17270). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in COL1A2 are known to be pathogenic (PMID: 2993307, 3372533, 6092353, 11288717, 15077201, 16816023, 27510842). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000018811 SCV000039094 pathogenic EHLERS-DANLOS SYNDROME, ARTHROCHALASIA TYPE, 2 2017-12-21 no assertion criteria provided literature only

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.