rs5743708
Positions:
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2
The NM_001318789.2(TLR2):c.2258G>A(p.Arg753Gln) variant causes a missense change. The variant allele was found at a frequency of 0.025 in 1,614,052 control chromosomes in the GnomAD database, including 632 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).
Frequency
Genomes: 𝑓 0.018 ( 40 hom., cov: 32)
Exomes 𝑓: 0.026 ( 592 hom. )
Consequence
TLR2
NM_001318789.2 missense
NM_001318789.2 missense
Scores
5
5
8
Clinical Significance
Conservation
PhyloP100: 6.79
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 -9 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.009150982).
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0177 (2699/152180) while in subpopulation NFE AF= 0.0294 (1998/67988). AF 95% confidence interval is 0.0283. There are 40 homozygotes in gnomad4. There are 1268 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
High Homozygotes in GnomAd4 at 40 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TLR2 | NM_001318789.2 | c.2258G>A | p.Arg753Gln | missense_variant | 3/3 | ENST00000642700.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TLR2 | ENST00000642700.2 | c.2258G>A | p.Arg753Gln | missense_variant | 3/3 | NM_001318789.2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0178 AC: 2701AN: 152062Hom.: 40 Cov.: 32
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GnomAD3 exomes AF: 0.0174 AC: 4375AN: 251060Hom.: 80 AF XY: 0.0173 AC XY: 2355AN XY: 135790
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GnomAD4 exome AF: 0.0257 AC: 37626AN: 1461872Hom.: 592 Cov.: 34 AF XY: 0.0250 AC XY: 18208AN XY: 727234
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GnomAD4 genome AF: 0.0177 AC: 2699AN: 152180Hom.: 40 Cov.: 32 AF XY: 0.0170 AC XY: 1268AN XY: 74394
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133
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ClinVar
Significance: risk factor
Submissions summary: Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Mycobacterium tuberculosis, susceptibility to Other:1
risk factor, no assertion criteria provided | literature only | OMIM | Nov 02, 2012 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;T;T;T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;.;.;D;T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M;M;.
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
.;.;.;D;.
REVEL
Benign
Sift
Pathogenic
.;.;.;D;.
Sift4G
Uncertain
.;.;.;D;.
Polyphen
D;D;D;D;.
Vest4
0.20
MPC
0.43
ClinPred
T
GERP RS
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at