Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001241102 | SCV001414096 | pathogenic | not provided | 2023-12-05 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ala895Serfs*49) in the COL2A1 gene. It is expected to result in an absent or disrupted protein product. 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 premature translational stop signal has been observed in individual(s) with Stickler syndrome and Kniest dysplasia (PMID: 20179744, 26626311, 26709265). ClinVar contains an entry for this variant (Variation ID: 966427). For these reasons, this variant has been classified as Pathogenic. |
Johns Hopkins Genomics, |
RCV001263467 | SCV001441541 | pathogenic | Stickler syndrome type 1 | 2020-11-03 | criteria provided, single submitter | clinical testing | This COL2A1 variant is absent from a large population database and has an entry in ClinVar. It has been reported in individuals affected with Stickler syndrome type I and Kniest dysplasia. This variant was detected in the paternal sample used for analysis. The reduced alternate allele fraction and suggestion of mild COL2A1-associated phenotypes suggest this variant is mosaic in the patient father. This frameshift variant occurs in exon 40 of 54 likely leading to nonsense-mediated decay and lack of protein production. We consider c.2678dupC to be pathogenic. |