Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002233686 | SCV000834586 | likely pathogenic | Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 | 2018-02-27 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 12 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 reported in an individual affected with osteogenesis imperfecta (PMID: 16705691). 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. 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, 16816023, 27510842). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Equipe Genetique des Anomalies du Developpement, |
RCV001526530 | SCV001736952 | pathogenic | Osteogenesis imperfecta | criteria provided, single submitter | clinical testing | ||
| Gene |
RCV003442054 | SCV004169906 | pathogenic | not provided | 2023-04-10 | criteria provided, single submitter | clinical testing | Reported in unrelated patients with osteogenesis imperfecta in published literature (Lee et al., 2006; Chen et al., 2022); patient-level clinical information not provided; Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; Damages or destroys the splice acceptor site in intron 12, and is expected to cause abnormal gene splicing; if the splice outcome is exon skip, the loss of the encoded residues in the triple helical region is expected to disrupt normal protein folding and function, and this is an established mechanism of disease (HGMD); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 35154279, 16705691) |