dbSNP rs5743704: TLR2:p.Pro631His (chr4-153704799-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001318789.2(TLR2):c.1892C>A(p.Pro631His) variant causes a missense change. The variant allele was found at a frequency of 0.0346 in 1,613,762 control chromosomes in the GnomAD database, including 1,139 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.027 ( 75 hom., cov: 32)

Exomes 𝑓: 0.035 ( 1064 hom. )

Consequence

TLR2
NM_001318789.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.09

Publications

107 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0063203275).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0275 (4173/151976) while in subpopulation NFE AF = 0.0414 (2815/67960). AF 95% confidence interval is 0.0401. There are 75 homozygotes in GnomAd4. There are 2008 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 75 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR2	NM_001318789.2 link	c.1892C>A	p.Pro631His	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.1892C>A	p.Pro631His	missense_variant	Exon 3 of 3		NM_001318789.2	ENSP00000494425.1		O60603

Frequencies

GnomAD3 genomes

AF:

0.0275

AC:

4176

AN:

151858

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00740

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.0170

Gnomad ASJ

AF:

0.0279

Gnomad EAS

AF:

0.000773

Gnomad SAS

AF:

0.0102

Gnomad FIN

AF:

0.0550

Gnomad MID

AF:

0.0191

Gnomad NFE

AF:

0.0414

Gnomad OTH

AF:

0.0182

GnomAD2 exomes

AF:

0.0278

AC:

6969

AN:

250972

AF XY:

0.0290

show subpopulations

Gnomad AFR exome

AF:

0.00690

Gnomad AMR exome

AF:

0.0115

Gnomad ASJ exome

AF:

0.0239

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.0550

Gnomad NFE exome

AF:

0.0391

Gnomad OTH exome

AF:

0.0271

GnomAD4 exome

AF:

0.0354

AC:

51696

AN:

1461786

Hom.:

1064

Cov.:

AF XY:

0.0349

AC XY:

25372

AN XY:

727192

show subpopulations

African (AFR)

AF:

0.00576

AC:

193

AN:

33480

American (AMR)

AF:

0.0124

AC:

554

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0226

AC:

591

AN:

26134

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39698

South Asian (SAS)

AF:

0.0135

AC:

1166

AN:

86254

European-Finnish (FIN)

AF:

0.0532

AC:

2841

AN:

53396

Middle Eastern (MID)

AF:

0.0283

AC:

163

AN:

5760

European-Non Finnish (NFE)

AF:

0.0398

AC:

44240

AN:

1111956

Other (OTH)

AF:

0.0322

AC:

1945

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

3235

6469

9704

12938

16173

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1582

3164

4746

6328

7910

<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:

0.0275

AC:

4173

AN:

151976

Hom.:

Cov.:

AF XY:

0.0270

AC XY:

2008

AN XY:

74274

show subpopulations

African (AFR)

AF:

0.00738

AC:

306

AN:

41452

American (AMR)

AF:

0.0170

AC:

259

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.0279

AC:

AN:

3472

East Asian (EAS)

AF:

0.000775

AC:

AN:

5160

South Asian (SAS)

AF:

0.0100

AC:

AN:

4780

European-Finnish (FIN)

AF:

0.0550

AC:

581

AN:

10562

Middle Eastern (MID)

AF:

0.0171

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0414

AC:

2815

AN:

67960

Other (OTH)

AF:

0.0180

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

199

398

596

795

994

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

156

208

260

<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:

0.0372

Hom.:

141

Bravo

AF:

0.0236

TwinsUK

AF:

0.0353

AC:

131

ALSPAC

AF:

0.0348

AC:

134

ESP6500AA

AF:

0.00704

AC:

ESP6500EA

AF:

0.0412

AC:

354

ExAC

AF:

0.0274

AC:

3327

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.0385

EpiControl

AF:

0.0383

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.43

T;T;T;T

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.97

.;.;.;D

MetaRNN

Benign

0.0063

T;T;T;T

MetaSVM

Benign

-0.76

MutationAssessor

Pathogenic

3.3

M;M;M;M

PhyloP100

4.1

PrimateAI

Benign

0.47

PROVEAN

Pathogenic

-4.9

.;.;.;D

REVEL

Benign

0.25

Sift

Uncertain

0.0010

.;.;.;D

Sift4G

Uncertain

0.0020

.;.;.;D

Polyphen

1.0

D;D;D;D

Vest4

0.18

MPC

0.43

ClinPred

0.028

GERP RS

5.7

Varity_R

0.62

gMVP

0.61

Mutation Taster

=93/7

polymorphism (auto)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over