ClinVar Miner

Submissions for variant NM_001285829.1(CEBPA):c.-38del (rs1600023511)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000809619 SCV000949781 likely pathogenic Acute myeloid leukemia 2018-12-07 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the CEBPA gene (p.Asp107Alafs*53). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 252 amino acids of the CEBPA protein. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has not been reported in the literature in individuals with CEBPA-related conditions. The region disrupted by this variant contains one transactivation domain (TAD2) and the basic zipper binding domain (bZip), which are required for CEBPA protein function (PMID: 11242107, 26162409). While experimental studies have not been reported for this specific variant, other experimental studies have shown that N-terminal frameshift variants that occur in the same region as this one can result in the preferential usage of an alternate downstream in-frame methionine at codon 120. Translation starting from this methionine results in a 30 kDa N-terminal truncated isoform of CEBPA that lacks the TAD1 domain, and has been shown to abrogate CEBPA function by acting as a dominant-negative allele (PMID: 11242107). 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.