ClinVar

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant has been observed in individual(s) with clinical features of autosomal dominant COL2A1-related conditions (Invitae). This variant is not present in population databases (gnomAD no frequency). This variant, c.2918_2926del, results in the deletion of 3 amino acid(s) of the COL2A1 protein (p.Pro973_Gly975del), but otherwise preserves the integrity of the reading frame.