Variant rs5743708 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The NM_001318789.2(TLR2):c.2258G>A(p.Arg753Gln) variant causes a missense change. The variant allele was found at a frequency of 0.025 in 1,614,052 control chromosomes in the GnomAD database, including 632 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

Frequency

Genomes: 𝑓 0.018 ( 40 hom., cov: 32)

Exomes 𝑓: 0.026 ( 592 hom. )

Consequence

TLR2
NM_001318789.2 missense

Scores

Clinical Significance

risk factor no assertion criteria provided O:1

Conservation

PhyloP100: 6.79

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 Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009150982).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0177 (2699/152180) while in subpopulation NFE AF= 0.0294 (1998/67988). AF 95% confidence interval is 0.0283. There are 40 homozygotes in gnomad4. There are 1268 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAd4 at 40 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLR2	NM_001318789.2 linkuse as main transcript	c.2258G>A	p.Arg753Gln	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.2258G>A	p.Arg753Gln	missense_variant	3/3		NM_001318789.2	P1

Frequencies

GnomAD3 genomes

AF:

0.0178

AC:

2701

AN:

152062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00418

Gnomad AMI

AF:

0.0231

Gnomad AMR

AF:

0.00831

Gnomad ASJ

AF:

0.00749

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.0299

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0294

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.0174

AC:

4375

AN:

251060

Hom.:

AF XY:

0.0173

AC XY:

2355

AN XY:

135790

show subpopulations

Gnomad AFR exome

AF:

0.00388

Gnomad AMR exome

AF:

0.00561

Gnomad ASJ exome

AF:

0.00746

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.00245

Gnomad FIN exome

AF:

0.0311

Gnomad NFE exome

AF:

0.0281

Gnomad OTH exome

AF:

0.0166

GnomAD4 exome

AF:

0.0257

AC:

37626

AN:

1461872

Hom.:

592

Cov.:

AF XY:

0.0250

AC XY:

18208

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00379

Gnomad4 AMR exome

AF:

0.00606

Gnomad4 ASJ exome

AF:

0.00765

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.00245

Gnomad4 FIN exome

AF:

0.0322

Gnomad4 NFE exome

AF:

0.0305

Gnomad4 OTH exome

AF:

0.0198

GnomAD4 genome

AF:

0.0177

AC:

2699

AN:

152180

Hom.:

Cov.:

AF XY:

0.0170

AC XY:

1268

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.00417

Gnomad4 AMR

AF:

0.00824

Gnomad4 ASJ

AF:

0.00749

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.0299

Gnomad4 NFE

AF:

0.0294

Gnomad4 OTH

AF:

0.0114

Alfa

AF:

0.0250

Hom.:

Bravo

AF:

0.0151

TwinsUK

AF:

0.0359

AC:

133

ALSPAC

AF:

0.0301

AC:

116

ESP6500AA

AF:

0.00522

AC:

ESP6500EA

AF:

0.0309

AC:

266

ExAC

AF:

0.0172

AC:

2093

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.0261

EpiControl

AF:

0.0219

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Mycobacterium tuberculosis, susceptibility to

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Nov 02, 2012

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.39

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.25

T;T;T;T;T

Eigen

Pathogenic

0.85

Eigen_PC

Pathogenic

0.83

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.86

.;.;.;D;T

MetaRNN

Benign

0.0092

T;T;T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.8

M;M;M;M;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-2.6

.;.;.;D;.

REVEL

Benign

0.24

Sift

Pathogenic

0.0

.;.;.;D;.

Sift4G

Uncertain

0.016

.;.;.;D;.

Polyphen

1.0

D;D;D;D;.

Vest4

0.20

MPC

0.43

ClinPred

0.014

GERP RS

5.6

Varity_R

0.81

gMVP

0.58

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over