Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001556675 | SCV001778299 | likely pathogenic | not provided | 2022-08-02 | criteria provided, single submitter | clinical testing | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge |
| Labcorp Genetics |
RCV001556675 | SCV002312748 | pathogenic | not provided | 2022-08-17 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1194069). This variant has not been reported in the literature in individuals affected with COL9A2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Asn503Thrfs*28) in the COL9A2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in COL9A2 are known to be pathogenic (PMID: 21671392, 33356723). |
| Clinical Genomics Laboratory, |
RCV003451810 | SCV004177066 | pathogenic | Stickler syndrome, type 5 | 2023-10-02 | criteria provided, single submitter | clinical testing | The COL9A2 c.1506del (p.Asn503ThrfsTer28) variant, to our knowledge, has not been reported in the medical literature but has been reported in the ClinVar database as a germline pathogenic or likely pathogenic variant by two submitters. This variant is only observed on 3/237,454 alleles in the general population (gnomAD v.2.1.1), indicating it is not a common variant. This variant causes a frameshift by deleting a single nucleotide, leading to a premature termination codon, which is predicted to lead to nonsense mediated decay. Additionally, other variants that introduce a premature termination codon downstream of this variant have been described in affected individuals and are considered pathogenic (ClinVar database; Nixon TRW et al., PMID: 31090205). Based on available information and the ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), this variant is classified as pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003485720 | SCV004242026 | pathogenic | Epiphyseal dysplasia, multiple, 2 | 2023-12-08 | criteria provided, single submitter | clinical testing | Variant summary: COL9A2 c.1506delG (p.Asn503ThrfsX28) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. This variant may be associated with dominant Epiphyseal dysplasia, multiple, 2 or recessive Stickler syndrome, type V. The variant allele was found at a frequency of 1.3e-05 in 237454 control chromosomes. To our knowledge, no occurrence of c.1506delG in individuals affected with Epiphyseal dysplasia, multiple, 2 or Stickler syndrome, type V, and no experimental evidence demonstrating its impact on protein function have been reported. Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |