Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001953550 | SCV002244225 | pathogenic | Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 | 2023-05-23 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the triple helix domain of COL1A2. Glycine residues within the Gly-Xaa-Yaa repeats of the triple helix domain are required for the structure and stability of fibrillar collagens (PMID: 7695699, 8218237, 19344236). In COL1A2, variants affecting these glycine residues are significantly enriched in individuals with disease (PMID: 9016532, 17078022) compared to the general population (ExAC). Studies have shown that disruption of this splice site results in skipping of exon 14, but is expected to preserve the integrity of the reading-frame (PMID: 17078022). ClinVar contains an entry for this variant (Variation ID: 1457016). This variant is also known as IVS14+2T>C . Disruption of this splice site has been observed in individual(s) with autosomal dominant osteogenesis imperfecta (PMID: 17078022). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 14 of the COL1A2 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in a shortened protein product. |