NM_018965.4(TREM2):c.97C>T (p.Gln33Ter) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 21, 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:: RCV002512810.9

Allele description

NM_018965.4(TREM2):c.97C>T (p.Gln33Ter)

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.97C>T (p.Gln33Ter)

HGVS:

NC_000006.12:g.41161557G>A
NG_011561.1:g.6628C>T
NM_001271821.2:c.97C>T
NM_018965.4:c.97C>TMANE SELECT
NP_001258750.1:p.Gln33Ter
NP_061838.1:p.Gln33Ter
LRG_631t1:c.97C>T
LRG_631:g.6628C>T
LRG_631p1:p.Gln33Ter
NC_000006.11:g.41129295G>A
NM_018965.2:c.97C>T
NM_018965.3:c.97C>T

Protein change:

Q33*; GLN33TER

Links:

OMIM: 605086.0007; dbSNP: rs104894002

NCBI 1000 Genomes Browser:

rs104894002

Molecular consequence:

NM_001271821.2:c.97C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_018965.4:c.97C>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV003439332	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 21, 2022)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 12080485, 12883936, 12925681, 23582655, 12754369, 23318515, 25615530, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003439332

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 21, 2022)

germline

clinical testing

PubMed (8)
[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

Mutations in two genes encoding different subunits of a receptor signaling complex result in an identical disease phenotype.

Paloneva J, Manninen T, Christman G, Hovanes K, Mandelin J, Adolfsson R, Bianchin M, Bird T, Miranda R, Salmaggi A, Tranebjaerg L, Konttinen Y, Peltonen L.

Am J Hum Genet. 2002 Sep;71(3):656-62. Epub 2002 Jun 21. Erratum in: Am J Hum Genet. 2003 Jan;72(1):225..

PubMed [citation]

PMID:: 12080485
PMCID:: PMC379202

An Italian family with Nasu-Hakola disease.

Salmaggi A, Maccagnano E, Musso A, Di Lena L, Paloneva J, Boiardi A.

J Neurol. 2003 Jul;250(7):878-80. No abstract available.

PubMed [citation]

PMID:: 12883936

See all PubMed Citations (8)

Details of each submission

From Invitae, SCV003439332.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

This sequence change creates a premature translational stop signal (p.Gln33*) in the TREM2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TREM2 are known to be pathogenic (PMID: 12080485, 12754369, 12883936, 12925681, 23318515, 23582655). This variant is present in population databases (rs104894002, gnomAD 0.006%). This premature translational stop signal has been observed in individuals with autosomal recessive TREM2-related conditions (PMID: 12754369, 23318515). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 5219). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this premature translational stop signal affects TREM2 function (PMID: 25615530). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic.

#	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: Sep 16, 2024

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