Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001245238 | SCV001418511 | pathogenic | Neonatal-onset encephalopathy with rigidity and seizures | 2023-12-19 | criteria provided, single submitter | clinical testing | This sequence change affects codon 465 of the BRAT1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the BRAT1 protein. This variant also falls at the last nucleotide of exon 10, which is part of the consensus splice site for this exon. This variant is present in population databases (rs201855243, gnomAD 0.005%). This variant has been observed in individual(s) with BRAT1-related conditions (PMID: 31618474, 31868227, 34747546). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 969810). Variants that disrupt 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. For these reasons, this variant has been classified as Pathogenic. |
| Gene |
RCV001587277 | SCV001823527 | pathogenic | not provided | 2021-11-29 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate p.(T465=) causes splice defects (Nuovo et al., 2021); Not observed at significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 30346566, 31868227, 34747546) |