ClinVar Miner

Submissions for variant NM_004364.5(CEBPA):c.646A>G (p.Thr216Ala)

dbSNP: rs1600022240
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000806293 SCV000946283 uncertain significance Acute myeloid leukemia 2023-08-24 criteria provided, single submitter clinical testing 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CEBPA protein function. ClinVar contains an entry for this variant (Variation ID: 651028). This variant has not been reported in the literature in individuals affected 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 gnomAD database. This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 216 of the CEBPA protein (p.Thr216Ala).
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV000806293 SCV004171421 uncertain significance Acute myeloid leukemia 2023-11-16 criteria provided, single submitter clinical testing The CEBPA c.646A>G (p.Thr216Ala) missense change is absent in gnomAD v2.1.1, however this data may be unreliable due to poor data quality at this location (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with familial acute myeloid leukemia. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.
Baylor Genetics RCV000806293 SCV004214798 uncertain significance Acute myeloid leukemia 2023-08-21 criteria provided, single submitter clinical testing

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