rs5743701
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001318789.2(TLR2):āc.1626C>Gā(p.Leu542=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00165 in 1,613,912 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0091 ( 14 hom., cov: 32)
Exomes š: 0.00087 ( 16 hom. )
Consequence
TLR2
NM_001318789.2 synonymous
NM_001318789.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.193
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
?
Variant 4-153704533-C-G is Benign according to our data. Variant chr4-153704533-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 776023.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.193 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00912 (1388/152194) while in subpopulation AFR AF= 0.0322 (1335/41516). AF 95% confidence interval is 0.0307. There are 14 homozygotes in gnomad4. There are 676 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 14 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TLR2 | NM_001318789.2 | c.1626C>G | p.Leu542= | synonymous_variant | 3/3 | ENST00000642700.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TLR2 | ENST00000642700.2 | c.1626C>G | p.Leu542= | synonymous_variant | 3/3 | NM_001318789.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00910 AC: 1384AN: 152076Hom.: 15 Cov.: 32
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GnomAD3 exomes AF: 0.00214 AC: 535AN: 250402Hom.: 7 AF XY: 0.00148 AC XY: 201AN XY: 135450
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GnomAD4 exome AF: 0.000867 AC: 1267AN: 1461718Hom.: 16 Cov.: 34 AF XY: 0.000744 AC XY: 541AN XY: 727154
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GnomAD4 genome ? AF: 0.00912 AC: 1388AN: 152194Hom.: 14 Cov.: 32 AF XY: 0.00909 AC XY: 676AN XY: 74408
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
TLR2-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 19, 2020 | 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). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Aug 16, 2018 | - - |
Colorectal cancer;C1834752:Mycobacterium tuberculosis, susceptibility to;C1968668:Leprosy, susceptibility to, 3 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Apr 05, 2022 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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