Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV002468973 | SCV002765193 | pathogenic | not provided | 2022-12-02 | criteria provided, single submitter | clinical testing | Canonical splice site variant in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 3403536) |
Invitae | RCV003764608 | SCV004569492 | pathogenic | Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 | 2024-01-16 | criteria provided, single submitter | clinical testing | This variant results in the deletion of part of exon 11 (c.487-4_501del) of the COL1A2 gene. 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 individuals with autosomal dominant osteogenesis imperfecta (PMID: 3403536; Invitae). This variant is also known as a 19-bp deletion that causes in-frame RNA splicing from the last codon of exon 10 to the first codon of exon 12 of the pro-d(I) gene. ClinVar contains an entry for this variant (Variation ID: 17237). Studies have shown that this variant results in skipping of exon 11, but is expected to preserve the integrity of the reading-frame (PMID: 3403536). 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 | RCV000018777 | SCV000039060 | pathogenic | Osteogenesis imperfecta, mild | 1988-08-15 | no assertion criteria provided | literature only |