chr4-153703149-T-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 1P and 3B. PP3BP4BP6_Moderate
The NM_001318789.2(TLR2):c.242T>C(p.Leu81Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000184 in 1,614,236 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00012 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00019 ( 2 hom. )
Consequence
TLR2
NM_001318789.2 missense
NM_001318789.2 missense
Scores
5
5
3
Clinical Significance
Conservation
PhyloP100: 5.37
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 Likely_benign. Variant got -2 ACMG points.
PP3
?
Multiple lines of computational evidence support a deleterious effect 6: AlphaMissense, BayesDel_noAF, Eigen, MutationAssessor, PROVEAN, REVEL [when max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]
BP4
?
Computational evidence support a benign effect (MetaRNN=0.27013785).
BP6
?
Variant 4-153703149-T-C is Benign according to our data. Variant chr4-153703149-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3046109.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TLR2 | NM_001318789.2 | c.242T>C | p.Leu81Pro | missense_variant | 3/3 | ENST00000642700.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TLR2 | ENST00000642700.2 | c.242T>C | p.Leu81Pro | missense_variant | 3/3 | NM_001318789.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000118 AC: 18AN: 152232Hom.: 0 Cov.: 31
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000346 AC: 87AN: 251222Hom.: 1 AF XY: 0.000420 AC XY: 57AN XY: 135764
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GnomAD4 exome AF: 0.000191 AC: 279AN: 1461886Hom.: 2 Cov.: 32 AF XY: 0.000254 AC XY: 185AN XY: 727244
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GnomAD4 genome ? AF: 0.000118 AC: 18AN: 152350Hom.: 0 Cov.: 31 AF XY: 0.000134 AC XY: 10AN XY: 74504
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
TLR2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 12, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
Cadd
Uncertain
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;.;.;.;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Pathogenic
D
MutationTaster
Benign
D
PrimateAI
Uncertain
T
Polyphen
1.0
.;D;D;D;D
Vest4
0.96
MVP
0.99
MPC
0.50
ClinPred
D
GERP RS
Varity_R
gMVP
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