rs5743699

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001318789.2(TLR2):c.1232C>T(p.Thr411Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00107 in 1,613,496 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0012 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 31 hom. )

Consequence

TLR2
NM_001318789.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.325

Publications

19 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0077039003).

BP6

Variant 4-153704139-C-T is Benign according to our data. Variant chr4-153704139-C-T is described in ClinVar as Benign. ClinVar VariationId is 3053334.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.00105 (1534/1461194) while in subpopulation AMR AF = 0.0278 (1240/44580). AF 95% confidence interval is 0.0265. There are 31 homozygotes in GnomAdExome4. There are 671 alleles in the male GnomAdExome4 subpopulation. Median coverage is 35. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR2	NM_001318789.2 link	c.1232C>T	p.Thr411Ile	missense_variant	Exon 3 of 3	ENST00000642700.2	NP_001305718.1	O60603A0A0S2Z4S4B3KWR9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR2	ENST00000642700.2 link	c.1232C>T	p.Thr411Ile	missense_variant	Exon 3 of 3		NM_001318789.2	ENSP00000494425.1		O60603

Frequencies

GnomAD3 genomes

AF:

0.00126

AC:

191

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00995

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00430

GnomAD2 exomes

AF:

0.00470

AC:

1173

AN:

249672

AF XY:

0.00364

show subpopulations

Gnomad AFR exome

AF:

0.0000632

Gnomad AMR exome

AF:

0.0308

Gnomad ASJ exome

AF:

0.00458

Gnomad EAS exome

AF:

0.00196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000796

Gnomad OTH exome

AF:

0.00345

GnomAD4 exome

AF:

0.00105

AC:

1534

AN:

1461194

Hom.:

Cov.:

AF XY:

0.000923

AC XY:

671

AN XY:

726828

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33432

American (AMR)

AF:

0.0278

AC:

1240

AN:

44580

Ashkenazi Jewish (ASJ)

AF:

0.00410

AC:

107

AN:

26126

East Asian (EAS)

AF:

0.00219

AC:

AN:

39686

South Asian (SAS)

AF:

0.0000582

AC:

AN:

85976

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000315

AC:

AN:

1111862

Other (OTH)

AF:

0.000928

AC:

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

160

241

321

401

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00125

AC:

190

AN:

152302

Hom.:

Cov.:

AF XY:

0.00132

AC XY:

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.000216

AC:

AN:

41574

American (AMR)

AF:

0.00987

AC:

151

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00231

AC:

AN:

3466

East Asian (EAS)

AF:

0.00135

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68024

Other (OTH)

AF:

0.00426

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000789

Hom.:

Bravo

AF:

0.00311

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00381

AC:

463

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TLR2-related disorder

Benign:1

Apr 05, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

T;T;T;T

Eigen

Uncertain

0.28

Eigen_PC

Benign

0.22

FATHMM_MKL

Benign

0.43

LIST_S2

Uncertain

0.94

.;.;.;D

MetaRNN

Benign

0.0077

T;T;T;T

MetaSVM

Benign

-0.77

MutationAssessor

Pathogenic

2.9

M;M;M;M

PhyloP100

0.33

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-3.2

.;.;.;D

REVEL

Benign

0.18

Sift

Benign

0.036

.;.;.;D

Sift4G

Benign

0.082

.;.;.;T

Polyphen

0.96

P;P;P;P

Vest4

0.29

MVP

0.84

MPC

0.40

ClinPred

0.050

GERP RS

5.4

Varity_R

0.16

gMVP

0.23

Mutation Taster

=94/6

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over