Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001373632 | SCV001570358 | uncertain significance | Familial acute necrotizing encephalopathy | 2020-04-24 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This sequence change affects codon 585 of the RANBP2 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the RANBP2 protein. This variant also falls at the last nucleotide of exon 12 of the RANBP2 coding sequence, which is part of the consensus splice site for this exon. This variant has not been reported in the literature in individuals with RANBP2-related conditions. 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. 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. |