NM_018965.4(TREM2):c.451G>A (p.Glu151Lys) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 18, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV002027521.2

Allele description [Variation Report for NM_018965.4(TREM2):c.451G>A (p.Glu151Lys)]

NM_018965.4(TREM2):c.451G>A (p.Glu151Lys)

Gene:

TREM2:triggering receptor expressed on myeloid cells 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6p21.1

Genomic location:

Preferred name:

NM_018965.4(TREM2):c.451G>A (p.Glu151Lys)

HGVS:

NC_000006.12:g.41159823C>T
NG_011561.1:g.8362G>A
NM_001271821.2:c.451G>A
NM_018965.4:c.451G>AMANE SELECT
NP_001258750.1:p.Glu151Lys
NP_061838.1:p.Glu151Lys
LRG_631:g.8362G>A
NC_000006.11:g.41127561C>T
NM_018965.2:c.451G>A

Protein change:

E151K

Links:

dbSNP: rs79011726

NCBI 1000 Genomes Browser:

rs79011726

Molecular consequence:

NM_001271821.2:c.451G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_018965.4:c.451G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002309600	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 18, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 25886450, 28620717, 32638105, 27589997, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002309600

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 18, 2022)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

TREM2 is associated with increased risk for Alzheimer's disease in African Americans.

Jin SC, Carrasquillo MM, Benitez BA, Skorupa T, Carrell D, Patel D, Lincoln S, Krishnan S, Kachadoorian M, Reitz C, Mayeux R, Wingo TS, Lah JJ, Levey AI, Murrell J, Hendrie H, Foroud T, Graff-Radford NR, Goate AM, Cruchaga C, Ertekin-Taner N.

Mol Neurodegener. 2015 Apr 10;10:19. doi: 10.1186/s13024-015-0016-9.

PubMed [citation]

PMID:: 25886450
PMCID:: PMC4426167

Multiple variants in families with amyotrophic lateral sclerosis and frontotemporal dementia related to C9orf72 repeat expansion: further observations on their oligogenic nature.

Giannoccaro MP, Bartoletti-Stella A, Piras S, Pession A, De Massis P, Oppi F, Stanzani-Maserati M, Pasini E, Baiardi S, Avoni P, Parchi P, Liguori R, Capellari S.

J Neurol. 2017 Jul;264(7):1426-1433. doi: 10.1007/s00415-017-8540-x. Epub 2017 Jun 15.

PubMed [citation]

PMID:: 28620717

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV002309600.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 151 of the TREM2 protein (p.Glu151Lys). This variant is present in population databases (rs79011726, gnomAD 0.05%). This missense change has been observed in individual(s) with TREM2-related conditions (PMID: 25886450, 28620717, 32638105). ClinVar contains an entry for this variant (Variation ID: 1517663). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The lysine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Experimental studies have shown that this missense change does not substantially affect TREM2 function (PMID: 27589997). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 1, 2024

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