ClinVar Miner

Submissions for variant NM_004364.5(CEBPA):c.1009A>T (p.Thr337Ser)

gnomAD frequency: 0.00003  dbSNP: rs587778192
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000533682 SCV000627077 uncertain significance Acute myeloid leukemia 2023-11-17 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 337 of the CEBPA protein (p.Thr337Ser). This variant is present in population databases (rs587778192, gnomAD 0.005%). This missense change has been observed in individual(s) with acute myeloid leukemia, but the germline nature of this variant is unclear (PMID: 28250006). ClinVar contains an entry for this variant (Variation ID: 133885). 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 RCV000120549 SCV002065351 uncertain significance not specified 2022-01-03 criteria provided, single submitter clinical testing DNA sequence analysis of the CEBPA gene demonstrated a sequence change, c.1009A>T, in exon 1 that results in an amino acid change, p.Thr337Ser. This sequence change has been described in the gnomAD database with a frequency of 0.005% in the non-Finnish European subpopulation (dbSNP rs587778192). The p.Thr337Ser change affects a highly conserved amino acid residue located in a domain of the CEBPA protein that is known to be functional. The p.Thr337Ser substitution appears to be benign using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). This sequence change does not appear to have been previously described in individuals with CEBPA-related disorders. Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Thr337Ser change remains unknown at this time.
GeneDx RCV002472950 SCV002770236 uncertain significance not provided 2023-08-01 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 31751678, 24728327, 28250006, 21455213)
Baylor Genetics RCV000533682 SCV004212549 uncertain significance Acute myeloid leukemia 2023-09-26 criteria provided, single submitter clinical testing
ITMI RCV000120549 SCV000084703 not provided not specified 2013-09-19 no assertion provided reference population

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