ClinVar Miner

Submissions for variant NM_004364.5(CEBPA):c.324C>G (p.Tyr108Ter)

dbSNP: rs1555742221
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001207644 SCV001379007 pathogenic Acute myeloid leukemia 2020-02-26 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the CEBPA gene (p.Tyr108*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 251 amino acids of the CEBPA protein. For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the CEBPA protein. Other variant(s) that disrupt this region (p.Glu148*) have been determined to be pathogenic (PMID: 29296967). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. This variant has not been reported in the literature in individuals with CEBPA-related conditions. 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.
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV001207644 SCV002526063 likely pathogenic Acute myeloid leukemia 2022-05-12 criteria provided, single submitter clinical testing The CEPBA c.324C>G (p.Tyr108Ter) change is a nonsense variant located in the CEBPA region encoding the N-terminal C/EBPα protein, which is predicted to produce a truncated protein (PVS1_strong; PMID: 30192042). This variant is absent in gnomAD v2.1.1 (PM2_supporting; https://gnomad.broadinstitute.org/). This variant has been identified in an individual with acute myeloid leukemia in which the tumor harbored a second somatic mutation affecting the C-terminus (PP4; internal data), a characteristic feature of germline CEBPA-associated acute myeloid leukemia (PMID: 26162409). In summary, this variant meets criteria to be classified as likely pathogenic based on the ACMG/AMP criteria applied: PVS1_strong, PM2_supporting, PP4.

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