dbSNP rs11938228: TLR2:c.-16-2098C>A (chr4-153700794-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001318789.2(TLR2):c.-16-2098C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 151,944 control chromosomes in the GnomAD database, including 8,943 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 0.32 ( 8943 hom., cov: 32)

Consequence

TLR2
NM_001318789.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.04

Publications

71 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318789.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TLR2	NM_001318789.2	MANE Select	c.-16-2098C>A	intron	N/A	NP_001305718.1	O60603
TLR2	NM_001318787.2		c.-300-1433C>A	intron	N/A	NP_001305716.1	A0A0S2Z4S4
TLR2	NM_001318790.2		c.-16-2098C>A	intron	N/A	NP_001305719.1	A0A0S2Z4S4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TLR2	ENST00000642700.2	MANE Select	c.-16-2098C>A	intron	N/A	ENSP00000494425.1	O60603
TLR2	ENST00000260010.7	TSL:6	c.-1408-706C>A	intron	N/A	ENSP00000260010.6	O60603
TLR2	ENST00000642580.1		c.-16-2098C>A	intron	N/A	ENSP00000495339.1	O60603

Frequencies

GnomAD3 genomes

AF:

0.325

AC:

49334

AN:

151826

Hom.:

8927

Cov.:

show subpopulations

Gnomad AFR

AF:

0.157

Gnomad AMI

AF:

0.560

Gnomad AMR

AF:

0.453

Gnomad ASJ

AF:

0.399

Gnomad EAS

AF:

0.411

Gnomad SAS

AF:

0.545

Gnomad FIN

AF:

0.364

Gnomad MID

AF:

0.358

Gnomad NFE

AF:

0.363

Gnomad OTH

AF:

0.314

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.325

AC:

49370

AN:

151944

Hom.:

8943

Cov.:

AF XY:

0.333

AC XY:

24748

AN XY:

74278

show subpopulations

African (AFR)

AF:

0.157

AC:

6506

AN:

41446

American (AMR)

AF:

0.454

AC:

6933

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.399

AC:

1382

AN:

3462

East Asian (EAS)

AF:

0.410

AC:

2122

AN:

5172

South Asian (SAS)

AF:

0.546

AC:

2632

AN:

4820

European-Finnish (FIN)

AF:

0.364

AC:

3835

AN:

10530

Middle Eastern (MID)

AF:

0.344

AC:

101

AN:

294

European-Non Finnish (NFE)

AF:

0.363

AC:

24679

AN:

67918

Other (OTH)

AF:

0.317

AC:

669

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1636

3272

4909

6545

8181

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

502

1004

1506

2008

2510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.348

Hom.:

19360

Bravo

AF:

0.321

Asia WGS

AF:

0.475

AC:

1648

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.22

(source)

DANN

Benign

0.68

PhyloP100

-1.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over