Submissions for variant NM_004364.5(CEBPA):c.388G>A (p.Gly130Ser)

gnomAD frequency: 0.00021  dbSNP: rs919904139

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000473665	SCV000548556	uncertain significance	Acute myeloid leukemia	2024-10-14	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 130 of the CEBPA protein (p.Gly130Ser). This variant is present in population databases (no rsID available, gnomAD 0.2%). 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: 408755). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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	RCV001821276	SCV002069373	uncertain significance	not specified	2018-07-30	criteria provided, single submitter	clinical testing
GeneDx	RCV002275032	SCV002562354	uncertain significance	not provided	2023-12-11	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; This variant is associated with the following publications: (PMID: 21455213)
Ambry Genetics	RCV002525573	SCV003702095	likely benign	Inborn genetic diseases	2024-10-18	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Baylor Genetics	RCV000473665	SCV004212542	uncertain significance	Acute myeloid leukemia	2023-12-29	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004755923	SCV005345094	likely benign	CEBPA-related disorder	2024-08-17	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).