Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: TET2

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 24 Feb 2025, 12:01 p.m. | Last Modified: 24 Feb 2025, 12:01 p.m.

Panel Version: 7.26

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

I don't know

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

Created: 1 Oct 2024, 10:58 a.m. | Last Modified: 14 Oct 2024, 2:34 p.m.

Panel Version: 6.16

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• PMID: 36066697

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.

Created: 4 Nov 2024, 12:07 p.m. | Last Modified: 4 Nov 2024, 12:07 p.m.

Panel Version: 7.4

Comment on phenotypes: This gene is now associated with a relevant phenotype in OMIM (Immunodeficiency 75, OMIM:619126)

Created: 4 Nov 2024, 11:52 a.m. | Last Modified: 4 Nov 2024, 11:52 a.m.

Panel Version: 7.2

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.

Created: 17 Sep 2020, 4:17 p.m. | Last Modified: 17 Sep 2020, 4:17 p.m.

Panel Version: 2.188

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.

Created: 17 Sep 2020, 4:14 p.m. | Last Modified: 17 Sep 2020, 4:14 p.m.

Panel Version: 2.187

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• 32518946

Green List (high evidence)

3 children with an immune dysregulation syndrome of susceptibility to infection, lymphadenopathy, hepatosplenomegaly, developmental delay, autoimmunity, and lymphoma of B-cell (n = 2) or T-cell (n = 1) origin, and bi-allelic variants in TET2.

Note mono-allelic variants in this gene have been associated with dementia and with germline susceptibility to myeloid malignancies, but evidence for these proposed associations is limited.

Created: 8 Sep 2020, 10:24 p.m. | Last Modified: 8 Sep 2020, 10:24 p.m.

Panel Version: 2.184

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Immune dysregulation; Lymphoma

Publications

• 32518946

Variants in this GENE are reported as part of current diagnostic practice

I don't know

Sources: Literature

Created: 3 Sep 2020, 3:08 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Primary Immunodeficiency; Lymphoma; Hepatosplenomegaly; Autoimmunity; Developmental delay

Publications

• 32518946