TET2
Basic information
Region (hg38): 4:105145875-105279816
Previous symbols: [ "KIAA1546" ]
Links
Phenotypes
GenCC
Source:
- immunodeficiency 75 (Strong), mode of inheritance: AR
- pulmonary arterial hypertension (Moderate), mode of inheritance: AD
Clinical Genomic Database
Source:
Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
---|---|---|---|---|---|
Immunodeficiency 75 with lymphoproliferation | AR | Allergy/Immunology/Infectious; Oncologic | Individuals 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 described | Allergy/Immunology/Infectious; Neurologic; Oncologic | 32518946 |
ClinVar
This is a list of variants' phenotypes submitted to
- 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 | 130 | 138 | ||||
missense | 238 | 11 | 17 | 267 | ||
nonsense | 18 | 33 | 53 | |||
start loss | 0 | |||||
frameshift | 32 | 24 | 59 | |||
inframe indel | 6 | |||||
splice donor/acceptor (+/-2bp) | 3 | |||||
splice region | 3 | 6 | 1 | 10 | ||
non coding | 14 | 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) | ||
4-105233951-G-A | not specified | Likely benign (Nov 28, 2024) | ||
4-105233952-G-T | not specified | Uncertain significance (Dec 04, 2024) | ||
4-105233957-A-G | not specified | Likely benign (Oct 15, 2024) | ||
4-105233963-C-T | Likely benign (Sep 05, 2023) | |||
4-105233964-C-G | Likely benign (Aug 09, 2022) | |||
4-105233978-C-T | Likely benign (Jun 15, 2018) | |||
4-105233979-A-C | not specified | Benign/Likely benign (Oct 02, 2024) | ||
4-105234002-A-C | Likely benign (Sep 01, 2023) | |||
4-105234016-G-T | not specified | Uncertain significance (Oct 04, 2024) | ||
4-105234022-C-G | Uncertain significance (Sep 15, 2022) | |||
4-105234028-C-G | not specified | Benign (Jan 31, 2024) | ||
4-105234037-C-T | Uncertain significance (Jan 25, 2022) | |||
4-105234042-C-T | not specified | Benign (Jan 31, 2024) | ||
4-105234055-G-T | Uncertain significance (Jun 02, 2022) | |||
4-105234058-C-T | Uncertain significance (Jun 07, 2022) | |||
4-105234109-C-G | not specified | Uncertain significance (Nov 27, 2024) | ||
4-105234113-C-T | not specified | Likely benign (Dec 09, 2024) | ||
4-105234122-T-C | Likely benign (Jul 19, 2023) | |||
4-105234138-A-T | Uncertain significance (Jul 16, 2023) | |||
4-105234139-T-C | not specified | not provided (Sep 19, 2013) | ||
4-105234159-C-T | not specified | Uncertain significance (Nov 28, 2024) | ||
4-105234162-G-A | not specified | Uncertain significance (Nov 21, 2024) | ||
4-105234171-G-A | not specified | Uncertain significance (Nov 30, 2024) | ||
4-105234176-T-A | not specified | Uncertain significance (Dec 06, 2024) |
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
TET2 | protein_coding | protein_coding | ENST00000540549 | 9 | 133942 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
4.33e-54 | 3.09e-10 | 125608 | 0 | 139 | 125747 | 0.000553 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | 1.62 | 872 | 1.02e+3 | 0.857 | 0.0000506 | 13154 |
Missense in Polyphen | 186 | 266.38 | 0.69825 | 3401 | ||
Synonymous | 1.49 | 341 | 378 | 0.902 | 0.0000192 | 3820 |
Loss of Function | -1.06 | 76 | 66.7 | 1.14 | 0.00000330 | 890 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.000861 | 0.000861 |
Ashkenazi Jewish | 0.00109 | 0.00109 |
East Asian | 0.000436 | 0.000435 |
Finnish | 0.000416 | 0.000416 |
European (Non-Finnish) | 0.000707 | 0.000659 |
Middle Eastern | 0.000436 | 0.000435 |
South Asian | 0.000294 | 0.000294 |
Other | 0.000659 | 0.000652 |
dbNSFP
Source:
- 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
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | Medium | Medium | Medium |
Primary Immunodeficiency | Medium | Medium | High |
Cancer | Medium | Medium | Medium |
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