ClinVar Miner

Submissions for variant NM_004364.5(CEBPA):c.715C>G (p.Pro239Ala)

gnomAD frequency: 0.00002  dbSNP: rs1162371435
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000631420 SCV000752493 uncertain significance Acute myeloid leukemia 2023-11-24 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 239 of the CEBPA protein (p.Pro239Ala). This variant is present in population databases (no rsID available, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with CEBPA-related conditions. ClinVar contains an entry for this variant (Variation ID: 526802). 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 with a negative predictive value of 80%. 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.
Genetic Services Laboratory, University of Chicago RCV001821788 SCV002066759 uncertain significance not specified 2021-01-08 criteria provided, single submitter clinical testing DNA sequence analysis of the CEBPA gene demonstrated a sequence change, c.715C>G, in exon 1 that results in an amino acid change, p.Pro239Ala. This sequence change does not appear to have been previously described in individuals with CEBPA-related disorders and has been described in the gnomAD database in two individuals with an overall population frequency of 0.0075% (dbSNP rs1162371435). The p.Pro239Ala change affects a moderately conserved amino acid residue located in a domain of the CEBPA protein that is known to be functional. The p.Pro239Ala substitution appears to be benign using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). Due to these contrasting evidences and the lack of functional studies, the clinical significance of the p.Pro239Ala change remains unknown at this time.
Fulgent Genetics, Fulgent Genetics RCV000631420 SCV002776800 uncertain significance Acute myeloid leukemia 2021-07-25 criteria provided, single submitter clinical testing
GeneDx RCV003327434 SCV004034454 uncertain significance not provided 2023-03-07 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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