ClinVar Miner

Submissions for variant NM_152743.4(BRAT1):c.1710del (p.Gln571fs) (rs756489141)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001008449 SCV001168220 likely pathogenic not provided 2018-11-26 criteria provided, single submitter clinical testing A variant that is likely pathogenic has been identified in the BRAT1 gene. The c.1710delG variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.1710delG variant causes a frameshift starting with codon Glutamine 571, changes this amino acid to a Serine residue and creates a premature Stop codon at position 32 of the new reading frame, denoted p.Gln571SerfsX32. This variant is predicted to cause loss of normal protein function through protein truncation as the last 251 amino acids are changed to 31 incorrect ones. The c.1710delG variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
Invitae RCV001237971 SCV001410764 likely pathogenic Rigidity and multifocal seizure syndrome, lethal neonatal 2019-07-23 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the BRAT1 gene (p.Gln571Serfs*32). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 251 amino acids of the BRAT1 protein. This variant is present in population databases (rs756489141, ExAC 0.02%). This variant has not been reported in the literature in individuals with BRAT1-related conditions. This variant disrupts the C-terminus of the BRAT1 protein. Other variant(s) that disrupt this region (p.Phe709Thrfs*17, p.Trp619*, p.Ser747Thrfs*36) have been observed in individuals with BRAT1-related conditions (PMID: 27480663, 28752061). This suggests that this may be a clinically significant region of the protein. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.