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rs3804100

Variant summary

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

The NM_001318789.2(TLR2):c.1350T>A(p.Ser450Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD Genomes project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S450S) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Consequence

TLR2
NM_001318789.2 missense

Scores

14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.21
Variant links:
Genes affected
TLR2 (HGNC:11848): (toll like receptor 2) The protein encoded by this gene is a member of the Toll-like receptor (TLR) family which plays a fundamental role in pathogen recognition and activation of innate immunity. TLRs are highly conserved from Drosophila to humans and share structural and functional similarities. This protein is a cell-surface protein that can form heterodimers with other TLR family members to recognize conserved molecules derived from microorganisms known as pathogen-associated molecular patterns (PAMPs). Activation of TLRs by PAMPs leads to an up-regulation of signaling pathways to modulate the host's inflammatory response. This gene is also thought to promote apoptosis in response to bacterial lipoproteins. This gene has been implicated in the pathogenesis of several autoimmune diseases. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

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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=0.051962048).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TLR2NM_001318789.2 linkuse as main transcriptc.1350T>A p.Ser450Arg missense_variant 3/3 ENST00000642700.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TLR2ENST00000642700.2 linkuse as main transcriptc.1350T>A p.Ser450Arg missense_variant 3/3 NM_001318789.2 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
35
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.39
T
BayesDel_noAF
Benign
-0.80
Cadd
Benign
0.0090
Dann
Benign
0.50
DEOGEN2
Benign
0.19
T;T;T;T
Eigen
Benign
-1.6
Eigen_PC
Benign
-1.7
FATHMM_MKL
Benign
0.038
N
M_CAP
Benign
0.0057
T
MetaRNN
Benign
0.052
T;T;T;T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
0.89
L;L;L;L
MutationTaster
Benign
1.0
P
PrimateAI
Benign
0.27
T
Polyphen
0.0030
B;B;B;B
Vest4
0.065
MutPred
0.43
Gain of MoRF binding (P = 0.0229);Gain of MoRF binding (P = 0.0229);Gain of MoRF binding (P = 0.0229);Gain of MoRF binding (P = 0.0229);
MVP
0.37
MPC
0.074
ClinPred
0.089
T
GERP RS
-11
Varity_R
0.084
gMVP
0.24

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs3804100; hg19: chr4-154625409; API