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Primary immunodeficiency or monogenic inflammatory bowel disease v7.26 TET2 Achchuthan Shanmugasundram Tag Q3_24_promote_green was removed from gene: TET2.
Tag Q3_24_NHS_review was removed from gene: TET2.
Primary immunodeficiency or monogenic inflammatory bowel disease v7.26 TET2 Achchuthan Shanmugasundram reviewed gene: TET2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v7.25 TET2 Achchuthan Shanmugasundram Source NHS GMS was added to TET2.
Source Expert Review Green was added to TET2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v7.4 TET2 Arina Puzriakova Tag Q3_24_promote_green tag was added to gene: TET2.
Tag Q3_24_NHS_review tag was added to gene: TET2.
Primary immunodeficiency or monogenic inflammatory bowel disease v7.4 TET2 Arina Puzriakova Classified gene: TET2 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v7.4 TET2 Arina Puzriakova Added comment: Comment on list classification: Total of at least 4 unrelated cases reported to date with an immune dysregulation syndrome and lymphoproliferation (PMIDs: 32518946; 36066697). Sufficient to promote this gene to green with biallelic MOI (3 cases) but not monoallelic (1 case) - possible that in trans variant was missed or the heterozygous variant in LRBA additionally detected in this individual acted as a phenotype-modifier.
Primary immunodeficiency or monogenic inflammatory bowel disease v7.4 TET2 Arina Puzriakova Gene: tet2 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v7.3 TET2 Arina Puzriakova Publications for gene: TET2 were set to 32518946
Primary immunodeficiency or monogenic inflammatory bowel disease v7.2 TET2 Arina Puzriakova Added comment: Comment on phenotypes: This gene is now associated with a relevant phenotype in OMIM (Immunodeficiency 75, OMIM:619126)
Primary immunodeficiency or monogenic inflammatory bowel disease v7.2 TET2 Arina Puzriakova Phenotypes for gene: TET2 were changed from Primary Immunodeficiency; Lymphoma; Hepatosplenomegaly; Autoimmunity; Developmental delay to Immunodeficiency 75, OMIM:619126
Primary immunodeficiency or monogenic inflammatory bowel disease v6.16 TET2 Sarah Dixon changed review comment from: PMID: 36066697 (2023) presents two additional patients with ALPS-like immune phenotypes. Inheritance pattern is not consistent between cases. Uncertain significance.

P1: lymphoproliferation, cytopenias, and immune dysregulation.
Biallelic truncating variants in TET2 identified, apparently germline, although notably neither variant was maternally inherited (father not available for testing).

P2: autoimmunity and lymphoproliferation
Apparently germline LOF variant in TET2 identified (monoallelic).; to: PMID: 36066697 (2023) presents two additional patients with ALPS-like immune phenotypes. Inheritance pattern is not consistent between cases. Uncertain significance.

P1: lymphoproliferation, cytopenias, and immune dysregulation.
Biallelic truncating variants in TET2 identified, apparently germline, although notably neither variant was maternally inherited (father not available for testing).

P2: autoimmunity and lymphoproliferation
Apparently germline LOF variant in TET2 identified (monoallelic).


PMID: 21803851
Tet2 knockout mouse model develops myeloid malignancy
Primary immunodeficiency or monogenic inflammatory bowel disease v6.10 TET2 Sarah Dixon reviewed gene: TET2: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 36066697; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v2.188 TET2 Arina Puzriakova changed review comment from: Comment on list classification: Additional cases required before inclusion of this gene on a diagnostic panel.

Rating Amber in anticipation of further publications/clinical evidence.; to: Comment on list classification: Additional cases required before inclusion of this gene on a diagnostic panel. Rating Amber in anticipation of further publications/clinical evidence.
Primary immunodeficiency or monogenic inflammatory bowel disease v2.188 TET2 Arina Puzriakova Classified gene: TET2 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v2.188 TET2 Arina Puzriakova Added comment: Comment on list classification: Additional cases required before inclusion of this gene on a diagnostic panel.

Rating Amber in anticipation of further publications/clinical evidence.
Primary immunodeficiency or monogenic inflammatory bowel disease v2.188 TET2 Arina Puzriakova Gene: tet2 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v2.187 TET2 Arina Puzriakova changed review comment from: PMID: 32518946 (2020) - Three cases from two unrelated consanguineous families with immunodeficiency and lymphoproliferative disease, associated with homozygous variants (c.4145A>G, p.H1382R and c.4894C>T,
p.Q1632*) in the TET2 gene. Molecular studies showed that the variants result in altered DNA methylation and B-cell maturation, as well as skewed T-cell differentiation and hematopoiesis.; to: PMID: 32518946 (2020) - Three cases from two unrelated consanguineous families with immunodeficiency and lymphoproliferative disease, associated with homozygous variants (c.4145A>G, p.H1382R and c.4894C>T, p.Q1632*) in the TET2 gene. Molecular studies showed that the variants result in altered DNA methylation and B-cell maturation, as well as skewed T-cell differentiation and hematopoiesis.
Primary immunodeficiency or monogenic inflammatory bowel disease v2.187 TET2 Arina Puzriakova reviewed gene: TET2: Rating: ; Mode of pathogenicity: None; Publications: 32518946; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v2.184 TET2 Zornitza Stark reviewed gene: TET2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32518946; Phenotypes: Immune dysregulation, Lymphoma; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Primary immunodeficiency or monogenic inflammatory bowel disease v2.184 TET2 Boaz Palterer gene: TET2 was added
gene: TET2 was added to Primary immunodeficiency. Sources: Literature
Mode of inheritance for gene: TET2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TET2 were set to 32518946
Phenotypes for gene: TET2 were set to Primary Immunodeficiency; Lymphoma; Hepatosplenomegaly; Autoimmunity; Developmental delay
Penetrance for gene: TET2 were set to unknown
Review for gene: TET2 was set to AMBER
Added comment: Sources: Literature