ClinVar Genomic variation as it relates to human health
NM_004364.5(CEBPA):c.724G>A (p.Gly242Ser)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_004364.5(CEBPA):c.724G>A (p.Gly242Ser)
Variation ID: 239927 Accession: VCV000239927.21
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 19q13.11 19: 33301691 (GRCh38) [ NCBI UCSC ] 19: 33792597 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Oct 16, 2017 May 12, 2024 Feb 1, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_004364.5:c.724G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_004355.2:p.Gly242Ser missense NM_001285829.2:c.367G>A NP_001272758.1:p.Gly123Ser missense NM_001287424.2:c.829G>A NP_001274353.1:p.Gly277Ser missense NM_001287435.2:c.682G>A NP_001274364.1:p.Gly228Ser missense NC_000019.10:g.33301691C>T NC_000019.9:g.33792597C>T NG_012022.1:g.5834G>A LRG_456:g.5834G>A LRG_456t1:c.724G>A - Protein change
- G242S, G123S, G228S, G277S
- Other names
- -
- Canonical SPDI
- NC_000019.10:33301690:C:T
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
-
0.00020 (T)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00000
1000 Genomes Project 30x 0.00016
1000 Genomes Project 0.00020
The Genome Aggregation Database (gnomAD) 0.00031
The Genome Aggregation Database (gnomAD), exomes 0.00033
Trans-Omics for Precision Medicine (TOPMed) 0.00035
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
---|---|---|---|---|---|---|
HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
CEBPA | No evidence available | No evidence available |
GRCh38 GRCh37 |
932 | 1002 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
---|---|---|---|---|
Uncertain significance (5) |
criteria provided, multiple submitters, no conflicts
|
Dec 17, 2023 | RCV000225808.16 | |
Autosomal dominant familial acute myeloid leukemia
|
not provided (1) |
no classification provided
|
- | RCV000509407.3 |
Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
|
Feb 1, 2024 | RCV002247675.7 | |
Uncertain significance (1) |
criteria provided, single submitter
|
Jun 19, 2019 | RCV001818614.5 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
---|---|---|---|---|---|
Uncertain significance
(Oct 31, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Acute myeloid leukemia
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV000896721.1
First in ClinVar: Mar 31, 2019 Last updated: Mar 31, 2019 |
|
|
Uncertain significance
(Jun 19, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: no
Allele origin:
germline
|
Genetic Services Laboratory, University of Chicago
Accession: SCV002064558.1
First in ClinVar: Jan 29, 2022 Last updated: Jan 29, 2022 |
|
|
Uncertain significance
(May 20, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV002520189.2
First in ClinVar: May 28, 2022 Last updated: Mar 04, 2023 |
Comment:
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 … (more)
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) (less)
|
|
Uncertain significance
(Feb 21, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Acute myeloid leukemia
Affected status: unknown
Allele origin:
germline
|
St. Jude Molecular Pathology, St. Jude Children's Research Hospital
Accession: SCV003843044.1
First in ClinVar: Mar 26, 2023 Last updated: Mar 26, 2023 |
Comment:
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 … (more)
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. (less)
|
|
Uncertain significance
(Dec 17, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Acute myeloid leukemia
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000288513.11
First in ClinVar: Jul 02, 2016 Last updated: Feb 28, 2024 |
Comment:
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). … (more)
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. (less)
|
|
Uncertain significance
(Oct 12, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Acute myeloid leukemia
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004212547.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
|
|
Uncertain significance
(Feb 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV004702792.3
First in ClinVar: Mar 10, 2024 Last updated: May 12, 2024 |
Number of individuals with the variant: 1
|
|
not provided
(-)
|
no classification provided
Method: phenotyping only
|
Autosomal dominant familial acute myeloid leukemia
Affected status: unknown
Allele origin:
unknown
|
GenomeConnect, ClinGen
Accession: SCV000607018.1
First in ClinVar: Oct 16, 2017 Last updated: Oct 16, 2017 |
Comment:
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 … (more)
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. (less)
Clinical Features:
Hyperthyroidism (present) , Type I diabetes mellitus (present) , Myopia (present) , Abnormality of vision (present) , Abnormality of eye movement (present) , Obsessive-compulsive behavior … (more)
Hyperthyroidism (present) , Type I diabetes mellitus (present) , Myopia (present) , Abnormality of vision (present) , Abnormality of eye movement (present) , Obsessive-compulsive behavior (present) , Depression (present) , Anxiety (present) , Stereotypy (present) , Hyperhidrosis (present) , Atrophic scars (present) , Abnormality of the curvature of the vertebral column (present) , Abnormality of the musculature of the limbs (present) , EMG abnormality (present) , Abnormality of muscle physiology (present) , Abnormality of the intestine (present) , Abnormality of the bladder (present) , Bruising susceptibility (present) (less)
Indication for testing: Diagnostic
Age: 40-49 years
Sex: female
Method: Confirmation technologies include any of the following: Sanger sequencing, Pacific Biosciences SMRT sequencing, MLPA, Array CGH. Array CGH confirmation of NGS CNV calling performed by Invitae Corporation
Testing laboratory: Invitae
Date variant was reported to submitter: 2016-06-10
Testing laboratory interpretation: Uncertain significance
|
|
not provided
(-)
|
no classification provided
Method: phenotyping only
|
Acute myeloid leukemia
Affected status: unknown
Allele origin:
unknown
|
GenomeConnect - Invitae Patient Insights Network
Accession: SCV004037519.1
First in ClinVar: Oct 07, 2023 Last updated: Oct 07, 2023 |
Comment:
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 … (more)
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. (less)
Clinical Features:
Family history of cancer (present) , Phenotypic abnormality (present)
Indication for testing: Diagnostic
Age: 40-49 years
Sex: female
Method: Gene Panel Sequencing
Testing laboratory: Invitae
Date variant was reported to submitter: 2016-06-10
Testing laboratory interpretation: Uncertain significance
|
Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
Molecular study of CEBPA in familial hematological malignancies. | El Abed R | Familial cancer | 2009 | PMID: 19731081 |
Text-mined citations for rs530569305 ...
HelpRecord last updated May 12, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.