Variant 4-153704257-T-C 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.1350T>C(p.Ser450=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0807 in 1,614,088 control chromosomes in the GnomAD database, including 6,660 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 0.071 ( 487 hom., cov: 32)

Exomes 𝑓: 0.082 ( 6173 hom. )

Consequence

TLR2
NM_001318789.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.21

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=-4.21 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.243 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.1350T>C	p.Ser450=	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.1350T>C	p.Ser450=	synonymous_variant	3/3		NM_001318789.2	ENSP00000494425	P1

Frequencies

GnomAD3 genomes

AF:

0.0711

AC:

10810

AN:

152128

Hom.:

487

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0530

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.0706

Gnomad ASJ

AF:

0.0646

Gnomad EAS

AF:

0.254

Gnomad SAS

AF:

0.149

Gnomad FIN

AF:

0.0333

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.0691

Gnomad OTH

AF:

0.0832

GnomAD3 exomes

AF:

0.0896

AC:

22502

AN:

251166

Hom.:

1453

AF XY:

0.0931

AC XY:

12635

AN XY:

135734

show subpopulations

Gnomad AFR exome

AF:

0.0516

Gnomad AMR exome

AF:

0.0675

Gnomad ASJ exome

AF:

0.0623

Gnomad EAS exome

AF:

0.259

Gnomad SAS exome

AF:

0.154

Gnomad FIN exome

AF:

0.0337

Gnomad NFE exome

AF:

0.0705

Gnomad OTH exome

AF:

0.0828

GnomAD4 exome

AF:

0.0817

AC:

119379

AN:

1461842

Hom.:

6173

Cov.:

AF XY:

0.0840

AC XY:

61061

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.0504

Gnomad4 AMR exome

AF:

0.0667

Gnomad4 ASJ exome

AF:

0.0582

Gnomad4 EAS exome

AF:

0.279

Gnomad4 SAS exome

AF:

0.154

Gnomad4 FIN exome

AF:

0.0355

Gnomad4 NFE exome

AF:

0.0729

Gnomad4 OTH exome

AF:

0.0862

GnomAD4 genome

AF:

0.0710

AC:

10815

AN:

152246

Hom.:

487

Cov.:

AF XY:

0.0731

AC XY:

5444

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0531

Gnomad4 AMR

AF:

0.0704

Gnomad4 ASJ

AF:

0.0646

Gnomad4 EAS

AF:

0.254

Gnomad4 SAS

AF:

0.149

Gnomad4 FIN

AF:

0.0333

Gnomad4 NFE

AF:

0.0691

Gnomad4 OTH

AF:

0.0833

Alfa

AF:

0.0733

Hom.:

997

Bravo

AF:

0.0729

Asia WGS

AF:

0.177

AC:

614

AN:

3478

EpiCase

AF:

0.0710

EpiControl

AF:

0.0730

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

Dec 09, 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

0.12

DANN

Benign

0.44

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