Variant rs5743702 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001318789.2(TLR2):c.1667T>C(p.Ile556Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000814 in 1,614,016 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 𝑓 0.00043 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00085 ( 1 hom. )

Consequence

TLR2
NM_001318789.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.43

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]

TLR2 links:

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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=0.0108784735).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLR2	NM_001318789.2 linkuse as main transcript	c.1667T>C	p.Ile556Thr	missense_variant	3/3	ENST00000642700.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLR2	ENST00000642700.2 linkuse as main transcript	c.1667T>C	p.Ile556Thr	missense_variant	3/3		NM_001318789.2	P1

Frequencies

GnomAD3 genomes

AF:

0.000428

AC:

AN:

152006

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000779

Gnomad OTH

AF:

0.000959

GnomAD3 exomes

AF:

0.000546

AC:

137

AN:

251030

Hom.:

AF XY:

0.000523

AC XY:

AN XY:

135704

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000376

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.000970

Gnomad OTH exome

AF:

0.000816

GnomAD4 exome

AF:

0.000854

AC:

1248

AN:

1461892

Hom.:

Cov.:

AF XY:

0.000831

AC XY:

604

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.000380

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.000243

Gnomad4 NFE exome

AF:

0.00103

Gnomad4 OTH exome

AF:

0.000911

GnomAD4 genome

AF:

0.000434

AC:

AN:

152124

Hom.:

Cov.:

AF XY:

0.000497

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000794

Gnomad4 OTH

AF:

0.000949

Alfa

AF:

0.000627

Hom.:

Bravo

AF:

0.000457

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000717

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00104

EpiControl

AF:

0.000652

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.047

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.0050

DANN

Benign

0.37

DEOGEN2

Benign

0.086

T;T;T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.82

.;.;.;T

M_CAP

Benign

0.0038

MetaRNN

Benign

0.011

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.63

N;N;N;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.25

PROVEAN

Benign

1.0

.;.;.;N

REVEL

Benign

0.0040

Sift

Benign

0.41

.;.;.;T

Sift4G

Benign

0.58

.;.;.;T

Polyphen

0.0

B;B;B;B

Vest4

0.0090

MVP

0.24

MPC

0.082

ClinPred

0.035

GERP RS

-3.7

Varity_R

0.044

gMVP

0.29

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over