TET2

tet methylcytosine dioxygenase 2, the group of Tet methylcytosine dioxygenase family

Basic information

Region (hg38): 4:105145875-105279816

Previous symbols: [ "KIAA1546" ]

Links

ENSG00000168769NCBI:54790OMIM:612839HGNC:25941Uniprot:Q6N021AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • immunodeficiency 75 (Strong), mode of inheritance: AR
  • pulmonary arterial hypertension (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Immunodeficiency 75 with lymphoproliferationARAllergy/Immunology/Infectious; OncologicIndividuals have been described with severe and early-onset infections, and awareness may allow early and aggressive management of infections; The condition can include hematologic malignancies, and awareness may allow early diagnosis and management; HSCT has been describedAllergy/Immunology/Infectious; Neurologic; Oncologic32518946

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TET2 gene.

  • not provided (49 variants)
  • Clonal hematopoiesis (1 variants)
  • Myelodysplastic syndrome (1 variants)
  • EBV-positive nodal T- and NK-cell lymphoma (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TET2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type Pathogenic Likely pathogenic VUS Likely benign Benign Sum
synonymous
1
clinvar
130
clinvar
7
clinvar
138
missense
1
clinvar
238
clinvar
11
clinvar
17
clinvar
267
nonsense
18
clinvar
2
clinvar
33
clinvar
53
start loss
0
frameshift
32
clinvar
3
clinvar
24
clinvar
59
inframe indel
6
clinvar
6
splice donor/acceptor (+/-2bp)
2
clinvar
1
clinvar
3
splice region
3
6
1
10
non coding
1
clinvar
14
clinvar
6
clinvar
21
Total 51 7 304 155 30

Highest pathogenic variant AF is 0.0000460

Variants in TET2

This is a list of pathogenic ClinVar variants found in the TET2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
4-105233833-TATAGATAG-T not specified Benign (Jan 24, 2024)1234506
4-105233951-G-A not specified Likely benign (Nov 28, 2024)2970734
4-105233952-G-T not specified Uncertain significance (Dec 04, 2024)3455369
4-105233957-A-G not specified Likely benign (Oct 15, 2024)2082675
4-105233963-C-T Likely benign (Sep 05, 2023)2918006
4-105233964-C-G Likely benign (Aug 09, 2022)2061159
4-105233978-C-T Likely benign (Jun 15, 2018)753440
4-105233979-A-C not specified Benign/Likely benign (Oct 02, 2024)2044059
4-105234002-A-C Likely benign (Sep 01, 2023)2870393
4-105234016-G-T not specified Uncertain significance (Oct 04, 2024)2899265
4-105234022-C-G Uncertain significance (Sep 15, 2022)1995846
4-105234028-C-G not specified Benign (Jan 31, 2024)135316
4-105234037-C-T Uncertain significance (Jan 25, 2022)1700440
4-105234042-C-T not specified Benign (Jan 31, 2024)135308
4-105234055-G-T Uncertain significance (Jun 02, 2022)1996923
4-105234058-C-T Uncertain significance (Jun 07, 2022)2002693
4-105234109-C-G not specified Uncertain significance (Nov 27, 2024)3455342
4-105234113-C-T not specified Likely benign (Dec 09, 2024)2708217
4-105234122-T-C Likely benign (Jul 19, 2023)3021870
4-105234138-A-T Uncertain significance (Jul 16, 2023)3010277
4-105234139-T-C not specified not provided (Sep 19, 2013)135322
4-105234159-C-T not specified Uncertain significance (Nov 28, 2024)3455345
4-105234162-G-A not specified Uncertain significance (Nov 21, 2024)3455306
4-105234171-G-A not specified Uncertain significance (Nov 30, 2024)3455355
4-105234176-T-A not specified Uncertain significance (Dec 06, 2024)3455378

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
TET2protein_codingprotein_codingENST00000540549 9133942
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
4.33e-543.09e-1012560801391257470.000553
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense1.628721.02e+30.8570.000050613154
Missense in Polyphen186266.380.698253401
Synonymous1.493413780.9020.00001923820
Loss of Function-1.067666.71.140.00000330890

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0008610.000861
Ashkenazi Jewish0.001090.00109
East Asian0.0004360.000435
Finnish0.0004160.000416
European (Non-Finnish)0.0007070.000659
Middle Eastern0.0004360.000435
South Asian0.0002940.000294
Other0.0006590.000652

dbNSFP

Source: dbNSFP

Function
FUNCTION: Dioxygenase that catalyzes the conversion of the modified genomic base 5-methylcytosine (5mC) into 5- hydroxymethylcytosine (5hmC) and plays a key role in active DNA demethylation. Has a preference for 5-hydroxymethylcytosine in CpG motifs. Also mediates subsequent conversion of 5hmC into 5- formylcytosine (5fC), and conversion of 5fC to 5-carboxylcytosine (5caC). Conversion of 5mC into 5hmC, 5fC and 5caC probably constitutes the first step in cytosine demethylation. Methylation at the C5 position of cytosine bases is an epigenetic modification of the mammalian genome which plays an important role in transcriptional regulation. In addition to its role in DNA demethylation, also involved in the recruitment of the O-GlcNAc transferase OGT to CpG-rich transcription start sites of active genes, thereby promoting histone H2B GlcNAcylation by OGT. {ECO:0000269|PubMed:19483684, ECO:0000269|PubMed:21057493, ECO:0000269|PubMed:21817016, ECO:0000269|PubMed:23222540, ECO:0000269|PubMed:23353889, ECO:0000269|PubMed:24315485}.;
Disease
DISEASE: Note=TET2 is frequently mutated in myeloproliferative disorders (MPD). These constitute a heterogeneous group of disorders, also known as myeloproliferative diseases or myeloproliferative neoplasms (MPN), characterized by cellular proliferation of one or more hematologic cell lines in the peripheral blood, distinct from acute leukemia. Included diseases are: essential thrombocythemia, polycythemia vera, primary myelofibrosis (chronic idiopathic myelofibrosis). Bone marrow samples from patients display uniformly low levels of hmC in genomic DNA compared to bone marrow samples from healthy controls as well as hypomethylation relative to controls at the majority of differentially methylated CpG sites.; DISEASE: Polycythemia vera (PV) [MIM:263300]: A myeloproliferative disorder characterized by abnormal proliferation of all hematopoietic bone marrow elements, erythroid hyperplasia, an absolute increase in total blood volume, but also by myeloid leukocytosis, thrombocytosis and splenomegaly. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=TET2 is frequently mutated in systemic mastocytosis; also known as systemic mast cell disease. A condition with features in common with myeloproliferative diseases. It is a clonal disorder of the mast cell and its precursor cells. The clinical symptoms and signs of systemic mastocytosis are due to accumulation of clonally derived mast cells in different tissues, including bone marrow, skin, the gastrointestinal tract, the liver, and the spleen.; DISEASE: Myelodysplastic syndrome (MDS) [MIM:614286]: A heterogeneous group of closely related clonal hematopoietic disorders. All are characterized by a hypercellular or hypocellular bone marrow with impaired morphology and maturation, dysplasia of the myeloid, megakaryocytic and/or erythroid lineages, and peripheral blood cytopenias resulting from ineffective blood cell production. Included diseases are: refractory anemia (RA), refractory anemia with ringed sideroblasts (RARS), refractory anemia with excess blasts (RAEB), refractory cytopenia with multilineage dysplasia and ringed sideroblasts (RCMD-RS); chronic myelomonocytic leukemia (CMML) is a myelodysplastic/myeloproliferative disease. MDS is considered a premalignant condition in a subgroup of patients that often progresses to acute myeloid leukemia (AML). {ECO:0000269|PubMed:19372255, ECO:0000269|PubMed:19483684, ECO:0000269|PubMed:21057493}. Note=The disease is caused by mutations affecting the gene represented in this entry. Bone marrow samples from patients display uniformly low levels of hmC in genomic DNA compared to bone marrow samples from healthy controls as well as hypomethylation relative to controls at the majority of differentially methylated CpG sites.;
Pathway
MECP2 and Associated Rett Syndrome;TET1,2,3 and TDG demethylate DNA;Epigenetic regulation of gene expression;Gene expression (Transcription) (Consensus)

Recessive Scores

pRec
0.0630

Intolerance Scores

loftool
0.998
rvis_EVS
1.97
rvis_percentile_EVS
97.56

Haploinsufficiency Scores

pHI
0.0619
hipred
N
hipred_score
0.123
ghis
0.426

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
N
gene_indispensability_score
0.0000286

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumHigh
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Tet2
Phenotype
renal/urinary system phenotype; immune system phenotype; liver/biliary system phenotype; neoplasm; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; growth/size/body region phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); cellular phenotype; endocrine/exocrine gland phenotype;

Zebrafish Information Network

Gene name
tet2
Affected structure
nucleate erythrocyte
Phenotype tag
abnormal
Phenotype quality
increased amount

Gene ontology

Biological process
5-methylcytosine catabolic process;protein O-linked glycosylation;cell cycle;response to organic cyclic compound;myeloid cell differentiation;positive regulation of transcription by RNA polymerase II;oxidation-reduction process;oxidative demethylation;DNA demethylation;histone H3-K4 trimethylation
Cellular component
nucleus
Molecular function
DNA binding;iron ion binding;protein binding;ferrous iron binding;zinc ion binding;methylcytosine dioxygenase activity