Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000598859 | SCV000709916 | pathogenic | not provided | 2019-05-22 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate that the c.1197+5 G>A results in skipping of exon 21 encoding Gly-X-Y repeats and the resulting protein showed intracellular retention (Nicholls et al., 1996); Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 25525159, 26177859, 17078022, 8829655, 28498836, 25944380, 27510842, 30715774, 31414283) |
| Invitae | RCV003766737 | SCV004569631 | pathogenic | Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 | 2023-09-10 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 21 of the COL1A2 gene. It does not directly change the encoded amino acid sequence of the COL1A2 protein. RNA analysis indicates that this variant induces altered splicing and likely results in a shortened protein product. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with autosomal dominant osteogenesis imperfecta (PMID: 17078022, 30715774). This variant is also known as g.17903G>A, IVS21+5G>A. ClinVar contains an entry for this variant (Variation ID: 425646). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of exon 21, but is expected to preserve the integrity of the reading-frame (PMID: 17078022). 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). For these reasons, this variant has been classified as Pathogenic. |
| OMIM | RCV002227169 | SCV000039088 | pathogenic | Osteogenesis imperfecta with normal sclerae, dominant form | 1996-01-01 | no assertion criteria provided | literature only | |
| Department of Medical Sciences, |
RCV000490711 | SCV000574648 | pathogenic | Osteogenesis imperfecta type I | no assertion criteria provided | clinical testing |