Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001320195 | SCV001510971 | pathogenic | not provided | 2022-09-23 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 16 of the COL2A1 gene. It does not directly change the encoded amino acid sequence of the COL2A1 protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 1020594). This variant has been observed in individual(s) with clinical features of autosomal dominant COL2A1-related conditions (Invitae). In at least one individual the variant was observed to be de novo. |
| Gene |
RCV001320195 | SCV001997365 | uncertain significance | not provided | 2020-01-02 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed in large population cohorts (Lek et al., 2016); In silico analysis predicts this variant damages or destroys the splice donor site in intron 16, which may cause abnormal gene splicing; if the splice outcome is exon skip, the loss of the encoded residues in the triple helical region is expected to disrupt normal protein folding and function, and this is an established mechanism of disease (Stenson et al., 2014); in the absence of RNA/functional studies, the actual effect of this sequence change is unknown |