Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000227901 | SCV000288502 | uncertain significance | Acute myeloid leukemia | 2024-11-04 | 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 340 of the CEBPA protein (p.Gly340Ser). This variant is present in population databases (rs375833261, gnomAD 0.006%). This missense change has been observed in individual(s) with acute myeloid leukemia and myelodysplastic syndrome (PMID: 14726504, 18768433, 24220272, 36879149). This variant is also known as 1609G>A and 1167G>A. ClinVar contains an entry for this variant (Variation ID: 239917). 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. |
| Baylor Genetics | RCV000227901 | SCV004212551 | uncertain significance | Acute myeloid leukemia | 2023-09-15 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV004721315 | SCV005327068 | uncertain significance | not provided | 2024-03-03 | criteria provided, single submitter | clinical testing | Observed in individuals with acute myeloid leukemia and myelodysplastic syndrome (PMID: 14726504, 18768433, 24220272, 29146883, 21177436, 37216690); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Also known as c.1164G>A; This variant is associated with the following publications: (PMID: 29146883, 14726504, 18768433, 24220272, 24448499, 19277035, 21177436, 36879149, 21455213, 37216690) |
| Ambry Genetics | RCV004965342 | SCV005558671 | likely benign | Inborn genetic diseases | 2024-08-23 | 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. |
| Prevention |
RCV004755820 | SCV005350414 | uncertain significance | CEBPA-related disorder | 2024-03-12 | no assertion criteria provided | clinical testing | The CEBPA c.1018G>A variant is predicted to result in the amino acid substitution p.Gly340Ser. This variant was reported in at least one individual with bone marrow failure (Bluteau et al. 2018. PubMed ID: 29146883). This variant is reported in 0.0071% of alleles in individuals of European (Non-Finnish) descent in gnomAD and is classified as variant of uncertain significance in Clinvar (https://www.ncbi.nlm.nih.gov/clinvar/variation/239917/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |