Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002231014 | SCV000627315 | pathogenic | Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 | 2017-06-16 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. 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: 9099837, 3372533). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has been reported to be de novo in an individual affected with osteogenesis imperfecta, type III (PMID: 26177859). It has also been reported in an individual affected with osteogenesis imperfecta, type IV (PMID: 16705691). This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 40 of the COL1A2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. |