Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002240406 | SCV001226966 | pathogenic | Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 | 2022-06-02 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. 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: 856673). Disruption of this splice site has been observed in individual(s) with osteogenesis imperfecta (PMID: 26177859; Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 40 of the COL1A2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in COL1A2 are known to be pathogenic (PMID: 11288717, 15077201). |