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rs3804099

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

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 Benign (★).

Frequency

Genomes: 𝑓 0.47 ( 17482 hom., cov: 32)
Exomes 𝑓: 0.43 ( 138179 hom. )

Consequence

TLR2
NM_001318789.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B: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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 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 [Benign]. Clinvar id is 3060911.Status of the report is criteria_provided_single_submitter, 1 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/exons MANE UniProt
TLR2NM_001318789.2 linkuse as main transcriptc.597T>C p.Asn199= synonymous_variant 3/3 ENST00000642700.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TLR2ENST00000642700.2 linkuse as main transcriptc.597T>C p.Asn199= synonymous_variant 3/3 NM_001318789.2 P1

Frequencies

GnomAD3 genomes
AF:
0.469
AC:
71322
AN:
151978
Hom.:
17450
Cov.:
32
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.:
51
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.:
32
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: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

TLR2-related condition Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesOct 16, 2019This 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.

Other links and lift over

dbSNP: rs3804099; hg19: chr4-154624656; COSMIC: COSV52606497; COSMIC: COSV52606497; API