Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001064457 | SCV001229361 | uncertain significance | Diamond-Blackfan anemia | 2022-10-04 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, and lead to utilization of a cryptic splice site located 3 nucleotides downstream. Use of this cryptic splice site would lead to an in-frame loss of 1 amino acid, but would otherwise preserve the integrity of the reading frame. An exon lacking this amino acid naturally occurs in an alternate isoform of RPL11 (NM_001199802.1). This prediction has not been confirmed by published transcriptional studies, but suggests that the clinical significance of this splice variant may be uncertain. 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: 858562). This variant has not been reported in the literature in individuals affected with RPL11-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 1 of the RPL11 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 RPL11 are known to be pathogenic (PMID: 19061985, 19773262). |