Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000598625 | SCV000709915 | pathogenic | not provided | 2021-12-21 | criteria provided, single submitter | clinical testing | Non-canonical splice site variant demonstrated to result in loss-of-function (Marini et al., 2007); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 17078022, 23692737, 31794058, 31141158) |
| Invitae | RCV002232565 | SCV000963024 | pathogenic | Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 | 2023-11-27 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 9 of the COL1A2 gene. It does not directly change the encoded amino acid sequence of the COL1A2 protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with clinical features of autosomal dominant Ehlers-Danlos syndrome and/or osteogenesis imperfecta (PMID: 17078022, 23692737, 31141158, 31794058; Invitae). This variant is also known as IVS9+4^7delAGTA. ClinVar contains an entry for this variant (Variation ID: 503685). 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. For these reasons, this variant has been classified as Pathogenic. |
| Neuberg Centre For Genomic Medicine, |
RCV004546528 | SCV005042818 | pathogenic | Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2 | criteria provided, single submitter | clinical testing | The splice site donor c.432+4_432+7del variant in the COL1A2 gene has been reported previously in patients affected with Osteogenesis Imperfecta/Ehlers-Danlos syndrome Morlino et al., 2020; Angwin et al., 2020. The variant is novel not in any individuals in 1000 Genomes and gnomAD. This sequence change falls in intron 9 of the COL1A2 gene. It is submitted to ClinVar with varying interpretations as Pathogenic/Likely Pathogenic. However functional evidence on the pathogenicity of the variant is unavailable. For these reasons, this variant has been classified as Likely Pathogenic. | |
| Biochemical Molecular Genetic Laboratory, |
RCV004545791 | SCV001132986 | pathogenic | COL1A2-related disorder | 2019-08-25 | no assertion criteria provided | clinical testing |