rs3804099

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001318789.2(TLR2):c.597T>C(p.Asn199Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 1,613,578 control chromosomes in the GnomAD database, including 155,661 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.47 ( 17482 hom., cov: 32)

Exomes 𝑓: 0.43 ( 138179 hom. )

Consequence

TLR2
NM_001318789.2 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity no assertion criteria provided U:1B:1

Conservation

PhyloP100: -0.718

Publications

324 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 4-153703504-T-C is Benign according to our data. Variant chr4-153703504-T-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 3060911.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.718 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.613 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR2	NM_001318789.2 link	c.597T>C	p.Asn199Asn	synonymous_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.597T>C	p.Asn199Asn	synonymous_variant	Exon 3 of 3		NM_001318789.2	ENSP00000494425.1		O60603

Frequencies

GnomAD3 genomes

AF:

0.469

AC:

71322

AN:

151978

Hom.:

17450

Cov.:

show subpopulations

Gnomad AFR

AF:

0.619

Gnomad AMI

AF:

0.328

Gnomad AMR

AF:

0.381

Gnomad ASJ

AF:

0.444

Gnomad EAS

AF:

0.287

Gnomad SAS

AF:

0.327

Gnomad FIN

AF:

0.379

Gnomad MID

AF:

0.446

Gnomad NFE

AF:

0.439

Gnomad OTH

AF:

0.479

GnomAD2 exomes

AF:

0.405

AC:

101488

AN:

250696

AF XY:

0.404

show subpopulations

Gnomad AFR exome

AF:

0.612

Gnomad AMR exome

AF:

0.326

Gnomad ASJ exome

AF:

0.434

Gnomad EAS exome

AF:

0.289

Gnomad FIN exome

AF:

0.375

Gnomad NFE exome

AF:

0.440

Gnomad OTH exome

AF:

0.423

GnomAD4 exome

AF:

0.432

AC:

630646

AN:

1461482

Hom.:

138179

Cov.:

AF XY:

0.429

AC XY:

311733

AN XY:

727018

show subpopulations

African (AFR)

AF:

0.617

AC:

20657

AN:

33468

American (AMR)

AF:

0.333

AC:

14879

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.431

AC:

11273

AN:

26126

East Asian (EAS)

AF:

0.304

AC:

12051

AN:

39676

South Asian (SAS)

AF:

0.332

AC:

28586

AN:

86160

European-Finnish (FIN)

AF:

0.376

AC:

20089

AN:

53360

Middle Eastern (MID)

AF:

0.454

AC:

2618

AN:

5768

European-Non Finnish (NFE)

AF:

0.445

AC:

494518

AN:

1111860

Other (OTH)

AF:

0.430

AC:

25975

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

21213

42425

63638

84850

106063

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14900

29800

44700

59600

74500

<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:

0.469

AC:

71398

AN:

152096

Hom.:

17482

Cov.:

AF XY:

0.461

AC XY:

34275

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.619

AC:

25680

AN:

41468

American (AMR)

AF:

0.380

AC:

5811

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.444

AC:

1540

AN:

3468

East Asian (EAS)

AF:

0.287

AC:

1488

AN:

5184

South Asian (SAS)

AF:

0.327

AC:

1576

AN:

4826

European-Finnish (FIN)

AF:

0.379

AC:

4009

AN:

10574

Middle Eastern (MID)

AF:

0.459

AC:

135

AN:

294

European-Non Finnish (NFE)

AF:

0.439

AC:

29862

AN:

67978

Other (OTH)

AF:

0.475

AC:

999

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1905

3810

5715

7620

9525

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

648

1296

1944

2592

3240

<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:

0.448

Hom.:

49344

Bravo

AF:

0.476

Asia WGS

AF:

0.305

AC:

1065

AN:

3478

EpiCase

AF:

0.444

EpiControl

AF:

0.439

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

COVID-19–associated multisystem inflammatory syndrome in adults

Uncertain:1

Jan 01, 2024

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:research

- -

TLR2-related disorder

Benign:1

Oct 16, 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

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.45

(source)

DANN

Benign

0.25

PhyloP100

-0.72

Mutation Taster

=100/0

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over