6-41161557-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018965.4(TREM2):​c.97C>A​(p.Gln33Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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: 6.8e-7 ( 0 hom. )

Consequence

TREM2
NM_018965.4 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.17
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06319812).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TREM2NM_018965.4 linkc.97C>A p.Gln33Lys missense_variant Exon 2 of 5 ENST00000373113.8 NP_061838.1 Q9NZC2-1Q5TCX1
TREM2NM_001271821.2 linkc.97C>A p.Gln33Lys missense_variant Exon 2 of 4 NP_001258750.1 Q9NZC2-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TREM2ENST00000373113.8 linkc.97C>A p.Gln33Lys missense_variant Exon 2 of 5 1 NM_018965.4 ENSP00000362205.3 Q9NZC2-1
TREM2ENST00000373122.8 linkc.97C>A p.Gln33Lys missense_variant Exon 2 of 5 1 ENSP00000362214.4 Q9NZC2-3
TREM2ENST00000338469.3 linkc.97C>A p.Gln33Lys missense_variant Exon 2 of 4 1 ENSP00000342651.4 Q9NZC2-2
ENSG00000290034ENST00000702590.1 linkn.364+5994G>T intron_variant Intron 2 of 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461744
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727186
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:
8.99e-7
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
AlphaMissense
Benign
0.082
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.70
CADD
Benign
11
DANN
Benign
0.63
DEOGEN2
Benign
0.074
.;T;.
Eigen
Benign
-1.0
Eigen_PC
Benign
-0.99
FATHMM_MKL
Benign
0.038
N
LIST_S2
Benign
0.60
T;T;T
M_CAP
Benign
0.0043
T
MetaRNN
Benign
0.063
T;T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
0.20
N;N;N
PrimateAI
Benign
0.23
T
PROVEAN
Benign
-0.25
N;N;N
REVEL
Benign
0.021
Sift
Benign
0.75
T;T;T
Sift4G
Benign
0.76
T;T;T
Polyphen
0.0030
B;B;B
Vest4
0.11
MutPred
0.42
Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);
MVP
0.13
MPC
0.19
ClinPred
0.032
T
GERP RS
-0.60
Varity_R
0.20
gMVP
0.34

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: chr6-41129295; API