Variant 4-153705250-G-A 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.2343G>A(p.Ala781=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00655 in 1,583,638 control chromosomes in the GnomAD database, including 1,062 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 0.013 ( 157 hom., cov: 32)

Exomes 𝑓: 0.0058 ( 905 hom. )

Consequence

TLR2
NM_001318789.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.37

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=-0.75).

BP7

Synonymous conserved (PhyloP=-1.37 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.117 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.2343G>A	p.Ala781=	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.2343G>A	p.Ala781=	synonymous_variant	3/3		NM_001318789.2	ENSP00000494425	P1

Frequencies

GnomAD3 genomes

AF:

0.0133

AC:

2016

AN:

152098

Hom.:

153

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00225

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.121

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00558

Gnomad SAS

AF:

0.000831

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.0130

GnomAD3 exomes

AF:

0.0274

AC:

6288

AN:

229482

Hom.:

725

AF XY:

0.0206

AC XY:

2565

AN XY:

124328

show subpopulations

Gnomad AFR exome

AF:

0.00148

Gnomad AMR exome

AF:

0.200

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00440

Gnomad SAS exome

AF:

0.000191

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000170

Gnomad OTH exome

AF:

0.0261

GnomAD4 exome

AF:

0.00583

AC:

8348

AN:

1431422

Hom.:

905

Cov.:

AF XY:

0.00496

AC XY:

3515

AN XY:

708868

show subpopulations

Gnomad4 AFR exome

AF:

0.00137

Gnomad4 AMR exome

AF:

0.193

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00446

Gnomad4 SAS exome

AF:

0.000145

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000100

Gnomad4 OTH exome

AF:

0.00566

GnomAD4 genome

AF:

0.0133

AC:

2030

AN:

152216

Hom.:

157

Cov.:

AF XY:

0.0158

AC XY:

1175

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.00224

Gnomad4 AMR

AF:

0.122

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00559

Gnomad4 SAS

AF:

0.000832

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.00380

Hom.:

Bravo

AF:

0.0230

Asia WGS

AF:

0.00693

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.30

DANN

Benign

0.77

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over