Overview

Pathogenicity: Alzheimer's Disease : Benign, Frontotemporal Dementia : Unclear Pathogenicity
Position: (GRCh38/hg38):Chr6:41161537 C>G
Position: (GRCh37/hg19):Chr6:41129275 C>G
dbSNP ID: rs200392967
Coding/Non-Coding: Coding
DNA Change: Substitution
Expected RNA Consequence: Substitution
Expected Protein Consequence: Missense
Codon Change: GAC to GAG
Reference Isoform: TREM2 Isoform 1 (230 aa)
Genomic Region: Exon 2

Findings

The D39E variant was found in one of 783 cognitively healthy controls and in none of 726 AD patients in a French study (Pottier et al., 2013). In a Belgian study, this variant was found in two of 1216 AD patients and in none of 359 FTD patients or 1094 cognitively healthy controls (Cuyvers et al., 2014). Subsequently, the variant was not associated with AD in a case-control study of more than 30,000 Caucasian subjects (odds ratio: 0.87, p = 0.8) (Sims et al., 2017).

Neuropathology

No data.

Biological Effect

This variant was predicted to be possibly damaging by Polyphen-2 (Cuyvers et al., 2014; Pottier et al., 2013), but to be tolerated by SIFT and neutral by SNPs&Go (Cuyvers et al., 2014).

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References

Paper Citations

1. Pottier C, Wallon D, Rousseau S, Rovelet-Lecrux A, Richard AC, Rollin-Sillaire A, Frebourg T, Campion D, Hannequin D. TREM2 R47H variant as a risk factor for early-onset Alzheimer's disease. J Alzheimers Dis. 2013;35(1):45-9. PubMed.
2. Cuyvers E, Bettens K, Philtjens S, Van Langenhove T, Gijselinck I, van der Zee J, Engelborghs S, Vandenbulcke M, Van Dongen J, Geerts N, Maes G, Mattheijssens M, Peeters K, Cras P, Vandenberghe R, De Deyn PP, Van Broeckhoven C, Cruts M, Sleegers K, BELNEU consortium. Investigating the role of rare heterozygous TREM2 variants in Alzheimer's disease and frontotemporal dementia. Neurobiol Aging. 2014 Mar;35(3):726.e11-9. Epub 2013 Oct 9 PubMed.
3. 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Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease. Nat Genet. 2017 Sep;49(9):1373-1384. Epub 2017 Jul 17 PubMed.

Further Reading

No Available Further Reading