Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001966406 | SCV002257054 | likely pathogenic | Ullrich congenital muscular dystrophy 2; Bethlem myopathy 2 | 2021-09-14 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 54 of the COL12A1 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 COL12A1 are known to be pathogenic (PMID: 24334604, 28973083). This variant is not present in population databases (ExAC no frequency). Disruption of this splice site has been observed in individual(s) with clinical features of autosomal dominant COL12A1-related conditions (PMID: 31273343; Invitae). In at least one individual the variant was observed to be de novo. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |