Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003783831 | SCV004571666 | likely pathogenic | Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 | 2023-06-14 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant has not been reported in the literature in individuals affected with COL1A2-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant results in the deletion of part of exon 11 (c.538_540+11del) 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 disease-causing for autosomal recessive COL1A2-related conditions (PMID: 15077201, 11288717). However, certain variants affecting donor or acceptor splice sites in the triple helical domain of COL1A2 are expected to result in in-frame exon skipping and have been reported to cause autosomal dominant COL1A2-related conditions (PMID: 17078022, 9295084). |