ClinVar Genomic variation as it relates to human health
NM_032638.5(GATA2):c.1084C>T (p.Arg362Ter)
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_032638.5(GATA2):c.1084C>T (p.Arg362Ter)
Variation ID: 435281 Accession: VCV000435281.17
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 3q21.3 3: 128481878 (GRCh38) [ NCBI UCSC ] 3: 128200721 (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 Aug 28, 2017 Mar 16, 2024 Feb 13, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_032638.5:c.1084C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_116027.2:p.Arg362Ter nonsense NM_001145661.2:c.1084C>T MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001139133.1:p.Arg362Ter nonsense NM_001145662.1:c.1042C>T NP_001139134.1:p.Arg348Ter nonsense NC_000003.12:g.128481878G>A NC_000003.11:g.128200721G>A NG_029334.1:g.16310C>T LRG_295:g.16310C>T LRG_295t1:c.1084C>T LRG_295t2:c.1084C>T LRG_295p2:p.Arg362Ter - Protein change
- R362*, R348*
- Other names
- p.Arg362*
- Canonical SPDI
- NC_000003.12:128481877:G:A
-
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.
-
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
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. |
|||
GATA2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
1481 | 1516 |
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. |
---|---|---|---|---|
Pathogenic (1) |
criteria provided, single submitter
|
Sep 24, 2015 | RCV000504503.6 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
|
Aug 28, 2023 | RCV000984822.10 | |
Likely pathogenic (1) |
criteria provided, single submitter
|
May 28, 2019 | RCV000987321.2 | |
Pathogenic (1) |
criteria provided, single submitter
|
Jul 6, 2021 | RCV001542118.2 | |
Pathogenic (1) |
criteria provided, single submitter
|
Oct 29, 2023 | RCV001857100.4 | |
Pathogenic (1) |
criteria provided, single submitter
|
Feb 13, 2024 | RCV003892022.1 |
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. |
|
---|---|---|---|---|---|
Pathogenic
(Sep 24, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
{Leukemia, acute myeloid, susceptibility to}
Affected status: yes
Allele origin:
germline
|
Genetic Services Laboratory, University of Chicago
Accession: SCV000594917.1
First in ClinVar: Aug 28, 2017 Last updated: Aug 28, 2017 |
|
|
Likely pathogenic
(May 28, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Deafness-lymphedema-leukemia syndrome
Affected status: unknown
Allele origin:
unknown
|
Mendelics
Accession: SCV001136587.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
|
|
Pathogenic
(Oct 23, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
(Unknown mechanism)
Affected status: yes
Allele origin:
germline
|
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001447529.1
First in ClinVar: Nov 28, 2020 Last updated: Nov 28, 2020 |
Clinical Features:
Neutropenia (present)
Sex: male
|
|
Pathogenic
(Jul 06, 2021)
|
criteria provided, single submitter
Method: curation
|
GATA2 deficiency with susceptibility to MDS/AML
Deafness-lymphedema-leukemia syndrome (Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Molecular Pathology Research Laboratory, SA Pathology
Accession: SCV001760786.1
First in ClinVar: Jul 24, 2021 Last updated: Jul 24, 2021 |
Comment:
PVS1, PS4, PM2
Number of individuals with the variant: 17
Clinical Features:
Myelodysplasia (present) , Acute Myeloid Leukemia (present) , Immunodeficiency (present) , Lymphedema (present) , Hematological abnormality (present)
|
|
Pathogenic
(Aug 28, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV004031779.1
First in ClinVar: Sep 09, 2023 Last updated: Sep 09, 2023 |
Comment:
Observed in individuals with a personal or family history consistent with pathogenic variants in this gene (Zhang 2015, Lovell 2016, Bluteau 2018, Donadieu 2018, Polat … (more)
Observed in individuals with a personal or family history consistent with pathogenic variants in this gene (Zhang 2015, Lovell 2016, Bluteau 2018, Donadieu 2018, Polat 2018, McReynolds 2019); Not observed at significant frequency in large population cohorts (gnomAD); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 27266944, 34670919, 32098966, 29146883, 25239263, 30578959, 29724903, 28440875, 30101490, 31753093, 30894283, 33363905, 28104920, 35753512, 34529785) (less)
|
|
Pathogenic
(Jan 03, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Not provided
Affected status: unknown
Allele origin:
germline
|
Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV004226760.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
Comment:
PP1, PM2_supporting, PM6, PS4_moderate, PVS1
Number of individuals with the variant: 8
|
|
Pathogenic
(Oct 29, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Monocytopenia with susceptibility to infections
Deafness-lymphedema-leukemia syndrome
Explanation for multiple conditions: Uncertain.
The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV002247448.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 28, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Arg362*) in the GATA2 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Arg362*) in the GATA2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GATA2 are known to be pathogenic (PMID: 21670465, 23223431). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with clinical features of GATA2-related conditions (PMID: 27266944, 29146883, 29724903, 32098966). ClinVar contains an entry for this variant (Variation ID: 435281). For these reasons, this variant has been classified as Pathogenic. (less)
|
|
Pathogenic
(Feb 13, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
GATA2-related condition
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV001132704.2
First in ClinVar: Dec 31, 2019 Last updated: Mar 16, 2024 |
Comment:
The GATA2 c.1084C>T variant is predicted to result in premature protein termination (p.Arg362*). This variant has been reported in a number of patients with GATA2-related … (more)
The GATA2 c.1084C>T variant is predicted to result in premature protein termination (p.Arg362*). This variant has been reported in a number of patients with GATA2-related disorders (see for example Donadieu et al. 2018. PubMed ID: 29724903; Bluteau et al. 2018. PubMed ID: 29146883). This variant is not present in a large population database (https://gnomad.broadinstitute.org/) and has been interpreted as Pathogenic/Likely pathogenic in the ClinVar database (https://www.ncbi.nlm.nih.gov/clinvar/variation/435281/). Nonsense variants in GATA2 are expected to be pathogenic. This variant is interpreted as pathogenic. (less)
|
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 |
---|---|---|---|---|
Clinical exome sequencing of 1000 families with complex immune phenotypes: Toward comprehensive genomic evaluations. | Similuk MN | The Journal of allergy and clinical immunology | 2022 | PMID: 35753512 |
ASXL1 and STAG2 are common mutations in GATA2 deficiency patients with bone marrow disease and myelodysplastic syndrome. | West RR | Blood advances | 2022 | PMID: 34529785 |
Combined Mutation of the GATA2 Gene and STAT5B Gene in a Patient with Hypogammaglobulinemia and Autoimmunity. | Liu Z | The Tohoku journal of experimental medicine | 2021 | PMID: 34670919 |
Many signs, one mutation: Early onset of de novo GATA2 deficiency syndrome. A case report. | Blanco ML | Clinical case reports | 2020 | PMID: 33363905 |
The complex genetic landscape of familial MDS and AML reveals pathogenic germline variants. | Rio-Machin A | Nature communications | 2020 | PMID: 32098966 |
[Congenital deaf-mutism with pale complexion and anemia for 1 year in a school-aged girl]. | Chen LL | Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics | 2019 | PMID: 31753093 |
GATA2 Deficiency in a Pediatric Patient. | Mojica AM | The journal of allergy and clinical immunology. In practice | 2019 | PMID: 30894283 |
MDS-associated mutations in germline GATA2 mutated patients with hematologic manifestations. | McReynolds LJ | Leukemia research | 2019 | PMID: 30578959 |
Folliculotropic mycosis fungoides associated with GATA2 deficiency: a new skin manifestation. | Fertitta L | The British journal of dermatology | 2018 | PMID: 30101490 |
Natural history of GATA2 deficiency in a survey of 79 French and Belgian patients. | Donadieu J | Haematologica | 2018 | PMID: 29724903 |
A landscape of germ line mutations in a cohort of inherited bone marrow failure patients. | Bluteau O | Blood | 2018 | PMID: 29146883 |
Skin manifestations among GATA2-deficient patients. | Polat A | The British journal of dermatology | 2018 | PMID: 28440875 |
Clinical utility of gene panel-based testing for hereditary myelodysplastic syndrome/acute leukemia predisposition syndromes. | Guidugli L | Leukemia | 2017 | PMID: 28104920 |
Persistent nodal histoplasmosis in nuclear factor kappa B essential modulator deficiency: Report of a case and review of infection in primary immunodeficiencies. | Lovell JP | The Journal of allergy and clinical immunology | 2016 | PMID: 27266944 |
Successful reduced-intensity stem cell transplantation for GATA2 deficiency before progression of advanced MDS. | Saida S | Pediatric transplantation | 2016 | PMID: 26748574 |
Prevalence, clinical characteristics, and prognosis of GATA2-related myelodysplastic syndromes in children and adolescents. | Wlodarski MW | Blood | 2016 | PMID: 26702063 |
Genomic analysis of bone marrow failure and myelodysplastic syndromes reveals phenotypic and diagnostic complexity. | Zhang MY | Haematologica | 2015 | PMID: 25239263 |
High frequency of GATA2 mutations in patients with mild chronic neutropenia evolving to MonoMac syndrome, myelodysplasia, and acute myeloid leukemia. | Pasquet M | Blood | 2013 | PMID: 23223431 |
Mutations in GATA2 are associated with the autosomal dominant and sporadic monocytopenia and mycobacterial infection (MonoMAC) syndrome. | Hsu AP | Blood | 2011 | PMID: 21670465 |
click to load more click to collapse |
Text-mined citations for rs1553770510 ...
HelpRecord last updated Mar 17, 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.