Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001876903 | SCV002127876 | pathogenic | Diamond-Blackfan anemia | 2021-04-20 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic. Disruption of this splice site has been observed in individual(s) with clinical features of Diamond-Blackfan anemia (PMID: 10590074,15384984, 25703294). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 3 of the RPS19 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 RPS19 are known to be pathogenic (PMID: 20960466). |