ClinVar Miner

Submissions for variant NM_001844.5(COL2A1):c.610-17_617del

dbSNP: rs2136619163
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Johns Hopkins Genomics, Johns Hopkins University 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 (formerly Invitae), Labcorp 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.

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