Variant rs3804099 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001318789.2(TLR2):c.597T>C(p.Asn199=) 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

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 -13 ACMG points.

BP4

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

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/exons	MANE	Protein	UniProt
TLR2	NM_001318789.2 linkuse as main transcript	c.597T>C	p.Asn199=	synonymous_variant	3/3	ENST00000642700.2	NP_001305718.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLR2	ENST00000642700.2 linkuse as main transcript	c.597T>C	p.Asn199=	synonymous_variant	3/3		NM_001318789.2	ENSP00000494425	P1

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

GnomAD3 exomes

AF:

0.405

AC:

101488

AN:

250696

Hom.:

21598

AF XY:

0.404

AC XY:

54735

AN XY:

135482

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 SAS exome

AF:

0.332

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

Gnomad4 AFR exome

AF:

0.617

Gnomad4 AMR exome

AF:

0.333

Gnomad4 ASJ exome

AF:

0.431

Gnomad4 EAS exome

AF:

0.304

Gnomad4 SAS exome

AF:

0.332

Gnomad4 FIN exome

AF:

0.376

Gnomad4 NFE exome

AF:

0.445

Gnomad4 OTH exome

AF:

0.430

GnomAD4 genome

AF:

0.469

AC:

71398

AN:

152096

Hom.:

17482

Cov.:

AF XY:

0.461

AC XY:

34275

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.619

Gnomad4 AMR

AF:

0.380

Gnomad4 ASJ

AF:

0.444

Gnomad4 EAS

AF:

0.287

Gnomad4 SAS

AF:

0.327

Gnomad4 FIN

AF:

0.379

Gnomad4 NFE

AF:

0.439

Gnomad4 OTH

AF:

0.475

Alfa

AF:

0.449

Hom.:

22637

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

Uncertain significance, no assertion criteria provided

research

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Jan 01, 2024

- -

TLR2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 16, 2019

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

DANN

Benign

0.25

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