Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000792669 | SCV000931978 | pathogenic | Diamond-Blackfan anemia | 2018-12-11 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in the last intron (intron 5) of the RPL11 gene. While this is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with Diamond-Blackfan anemia (PMID: 19773262, Invitae). In one of these individuals, it has been observed to be de novo (Invitae). Nucleotide substitutions within 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, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic. |