Submissions for variant NM_004364.5(CEBPA):c.724G>A (p.Gly242Ser)

gnomAD frequency: 0.00031  dbSNP: rs530569305

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000225808	SCV000288513	uncertain significance	Acute myeloid leukemia	2023-12-17	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 242 of the CEBPA protein (p.Gly242Ser). This variant is present in population databases (rs530569305, gnomAD 0.03%). This missense change has been observed in individual(s) with familial hematological malignancies with solid tumors (PMID: 19731081). ClinVar contains an entry for this variant (Variation ID: 239927). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.
Fulgent Genetics, Fulgent Genetics	RCV000225808	SCV000896721	uncertain significance	Acute myeloid leukemia	2018-10-31	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV001818614	SCV002064558	uncertain significance	not specified	2019-06-19	criteria provided, single submitter	clinical testing
GeneDx	RCV002247675	SCV002520189	uncertain significance	not provided	2022-05-20	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Observed in an individual with chronic lymphocytic leukemia (El Abed 2009); This variant is associated with the following publications: (PMID: 19731081)
St. Jude Molecular Pathology, St. Jude Children's Research Hospital	RCV000225808	SCV003843044	uncertain significance	Acute myeloid leukemia	2023-02-21	criteria provided, single submitter	clinical testing	The CEBPA c.724G>A (p.Gly242Ser) missense change has a maximum subpopulation frequency of 0.031% in gnomAD v2.1.1 (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. This variant has been reported in an individual diagnosed with chronic lymphocytic leukemia with a family history of hematological malignancies and solid tumors (PMID: 19731081). 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	RCV000225808	SCV004212547	uncertain significance	Acute myeloid leukemia	2023-10-12	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV002247675	SCV004702792	uncertain significance	not provided	2024-02-01	criteria provided, single submitter	clinical testing
GenomeConnect, ClinGen	RCV000509407	SCV000607018	not provided	Autosomal dominant familial acute myeloid leukemia		no assertion provided	phenotyping only	GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
GenomeConnect - Invitae Patient Insights Network	RCV000225808	SCV004037519	not provided	Acute myeloid leukemia		no assertion provided	phenotyping only	Variant classified as Uncertain significance and reported on 06-10-2016 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.