TREM2
Basic information
Region (hg38): 6:41158506-41163186
Links
Phenotypes
GenCC
Source:
- polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2 (Strong), mode of inheritance: AR
- polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2 (Strong), mode of inheritance: AR
- polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2 (Moderate), mode of inheritance: AR
- polycystic lipomembranous osteodysplasia with sclerosing leukoencephaly (Supportive), mode of inheritance: AR
- polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2 (Strong), mode of inheritance: AR
Clinical Genomic Database
Source:
Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
---|---|---|---|---|---|
Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2 (Nasu-Hakola disease); Early-onset dementia without bone cysts | AR | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Musculoskeletal; Neurologic | 12080485; 15883308; 1854636; 21834902; 23318515 |
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (6 variants)
- Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1 (4 variants)
- Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2 (3 variants)
- Frontotemporal dementia (1 variants)
- Inborn genetic diseases (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the TREM2 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 | 26 | 29 | ||||
missense | 68 | 13 | 87 | |||
nonsense | 7 | |||||
start loss | 0 | |||||
frameshift | 4 | |||||
inframe indel | 0 | |||||
splice donor/acceptor (+/-2bp) | 3 | |||||
splice region | 1 | 3 | 4 | |||
non coding | 14 | 19 | ||||
Total | 9 | 10 | 73 | 54 | 3 |
Highest pathogenic variant AF is 0.0000197
Variants in TREM2
This is a list of pathogenic ClinVar variants found in the TREM2 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
Position | Type | Phenotype | Significance | ClinVar |
---|---|---|---|---|
6-41158595-C-T | TREM2-related disorder | Likely benign (Jul 31, 2019) | ||
6-41158607-C-T | Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2 | Uncertain significance (May 21, 2021) | ||
6-41158608-C-A | Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2 | Uncertain significance (Oct 05, 2022) | ||
6-41158616-G-A | Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2 | Uncertain significance (Jan 18, 2024) | ||
6-41158641-G-A | Uncertain significance (May 27, 2022) | |||
6-41158650-G-A | Likely benign (Aug 03, 2021) | |||
6-41158653-T-C | Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1 | Uncertain significance (Jun 14, 2016) | ||
6-41158655-G-C | Uncertain significance (Dec 02, 2021) | |||
6-41158656-TC-CT | Uncertain significance (Oct 03, 2023) | |||
6-41158657-C-A | Conflicting classifications of pathogenicity (Dec 07, 2023) | |||
6-41158659-C-G | Uncertain significance (Dec 24, 2021) | |||
6-41158662-G-C | Uncertain significance (May 07, 2022) | |||
6-41158663-C-G | Uncertain significance (Aug 17, 2023) | |||
6-41158684-T-A | Likely benign (Dec 22, 2023) | |||
6-41158691-C-T | Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2 • not specified | Benign/Likely benign (Oct 01, 2024) | ||
6-41158694-G-A | Likely benign (Jul 17, 2022) | |||
6-41158703-A-G | Uncertain significance (Apr 25, 2022) | |||
6-41158711-T-A | Uncertain significance (Mar 11, 2022) | |||
6-41158716-T-A | Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2 | Benign/Likely benign (Aug 24, 2023) | ||
6-41158719-T-A | Uncertain significance (Aug 31, 2022) | |||
6-41158719-T-C | Uncertain significance (May 12, 2022) | |||
6-41158721-C-G | Uncertain significance (Aug 07, 2022) | |||
6-41158734-C-T | Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2 • TREM2-related disorder | Benign (Dec 22, 2023) | ||
6-41158738-T-C | Uncertain significance (May 16, 2022) | |||
6-41158762-C-T | TREM2-related disorder | Likely benign (Dec 26, 2023) |
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
TREM2 | protein_coding | protein_coding | ENST00000373113 | 5 | 4681 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
3.29e-9 | 0.0506 | 125720 | 0 | 28 | 125748 | 0.000111 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | 0.245 | 125 | 133 | 0.940 | 0.00000760 | 1481 |
Missense in Polyphen | 44 | 43.168 | 1.0193 | 495 | ||
Synonymous | 1.27 | 46 | 58.4 | 0.788 | 0.00000353 | 480 |
Loss of Function | -0.518 | 12 | 10.2 | 1.17 | 4.41e-7 | 105 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.000145 | 0.000145 |
Ashkenazi Jewish | 0.00 | 0.00 |
East Asian | 0.000109 | 0.000109 |
Finnish | 0.000141 | 0.000139 |
European (Non-Finnish) | 0.000133 | 0.000132 |
Middle Eastern | 0.000109 | 0.000109 |
South Asian | 0.0000980 | 0.0000980 |
Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Forms a receptor signaling complex with TYROBP and triggers activation of the immune responses in macrophages and dendritic cells. May have a role in chronic inflammations and may stimulate production of constitutive rather than inflammatory chemokines and cytokines. {ECO:0000269|PubMed:10799849}.;
- Pathway
- Osteoclast differentiation - Homo sapiens (human);Microglia Pathogen Phagocytosis Pathway;Developmental Biology;DAP12 signaling;DAP12 interactions;Innate Immune System;Immune System;Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell;Adaptive Immune System;Other semaphorin interactions;Semaphorin interactions;Axon guidance;RANKL
(Consensus)
Recessive Scores
- pRec
- 0.155
Intolerance Scores
- loftool
- 0.838
- rvis_EVS
- 0.48
- rvis_percentile_EVS
- 79.25
Haploinsufficiency Scores
- pHI
- 0.0439
- hipred
- N
- hipred_score
- 0.123
- ghis
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.0196
Gene Damage Prediction
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | Medium | Medium | Medium |
Primary Immunodeficiency | Medium | Medium | Medium |
Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Trem2
- Phenotype
- immune system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); 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); hematopoietic system phenotype; cellular phenotype; homeostasis/metabolism phenotype;
Gene ontology
- Biological process
- positive regulation of antigen processing and presentation of peptide antigen via MHC class II;phagocytosis, engulfment;humoral immune response;osteoclast differentiation;detection of lipopolysaccharide;detection of peptidoglycan;innate immune response;positive regulation of peptidyl-tyrosine phosphorylation;regulation of immune response;positive regulation of calcium-mediated signaling;positive regulation of ERK1 and ERK2 cascade;detection of lipoteichoic acid;cellular response to lipoteichoic acid;cellular response to peptidoglycan;dendritic cell differentiation;positive regulation of protein localization to plasma membrane;positive regulation of C-C chemokine receptor CCR7 signaling pathway;positive regulation of CD40 signaling pathway
- Cellular component
- extracellular region;plasma membrane;integral component of membrane
- Molecular function
- lipopolysaccharide binding;phospholipid binding;signaling receptor activity;peptidoglycan binding;lipoteichoic acid binding;scaffold protein binding