Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Johns Hopkins Genomics, |
RCV001543669 | SCV001762356 | likely pathogenic | Stickler syndrome type 1 | 2021-07-27 | criteria provided, single submitter | clinical testing | COL2A1 c.610-17_617del is absent from a large population dataset and has not been reported in ClinVar nor the literature, to our knowledge. This variant deletes the native acceptor (3') splice site for exon 9 and is predicted to cause aberrant mRNA splicing. We consider COL2A1 c.610-17_617del to be likely pathogenic. |
Labcorp Genetics |
RCV002570662 | SCV003333484 | pathogenic | not provided | 2023-11-14 | criteria provided, single submitter | clinical testing | This variant results in the deletion of part of exon 9 (c.610-17_617del) of the COL2A1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in COL2A1 are known to be pathogenic (PMID: 20179744). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with COL2A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1185019). This variant disrupts the triple helix domain of COL2A1. 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 COL2A1, 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. |