ENST00000338469.3:c.604G>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2

The ENST00000338469.3(TREM2):​c.604G>T​(p.Glu202*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,456,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TREM2
ENST00000338469.3 stop_gained

Scores

7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.948
Variant links:
Genes affected
TREM2 (HGNC:17761): (triggering receptor expressed on myeloid cells 2) This gene encodes a membrane protein that forms a receptor signaling complex with the TYRO protein tyrosine kinase binding protein. The encoded protein functions in immune response and may be involved in chronic inflammation by triggering the production of constitutive inflammatory cytokines. Defects in this gene are a cause of polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Nov 2012]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0848 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TREM2NM_018965.4 linkc.*105G>T 3_prime_UTR_variant Exon 5 of 5 ENST00000373113.8 NP_061838.1 Q9NZC2-1Q5TCX1
TREM2NM_001271821.2 linkc.604G>T p.Glu202* stop_gained Exon 4 of 4 NP_001258750.1 Q9NZC2-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TREM2ENST00000338469.3 linkc.604G>T p.Glu202* stop_gained Exon 4 of 4 1 ENSP00000342651.4 Q9NZC2-2
TREM2ENST00000373113 linkc.*105G>T 3_prime_UTR_variant Exon 5 of 5 1 NM_018965.4 ENSP00000362205.3 Q9NZC2-1
TREM2ENST00000373122 linkc.*169G>T 3_prime_UTR_variant Exon 5 of 5 1 ENSP00000362214.4 Q9NZC2-3
ENSG00000290034ENST00000702590.1 linkn.364+3096C>A intron_variant Intron 2 of 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1456652
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
723970
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.82
CADD
Benign
7.7
DANN
Benign
0.96
Eigen
Benign
-0.57
Eigen_PC
Benign
-0.70
FATHMM_MKL
Benign
0.043
N
Vest4
0.11
GERP RS
2.4

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-41126397; API