Genetic Variant TLR2:c.-17+324T>C (chr4-153688371-T-C) – 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.-17+324T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.802 in 152,342 control chromosomes in the GnomAD database, including 50,159 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 0.80 ( 50065 hom., cov: 31)

Exomes 𝑓: 0.86 ( 94 hom. )

Consequence

TLR2
NM_001318789.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.87

Publications

55 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=-0.93).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 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
TLR2	NM_001318789.2	MANE Select	c.-17+324T>C	intron	N/A	NP_001305718.1
TLR2	NM_001318787.2		c.-301+383T>C	intron	N/A	NP_001305716.1
TLR2	NM_001318790.2		c.-17+324T>C	intron	N/A	NP_001305719.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TLR2	ENST00000642700.2	MANE Select	c.-17+324T>C	intron	N/A	ENSP00000494425.1
TLR2	ENST00000645889.1		n.437T>C	non_coding_transcript_exon	Exon 3 of 3
TLR2	ENST00000260010.7	TSL:6	c.-1409+324T>C	intron	N/A	ENSP00000260010.6

Frequencies

GnomAD3 genomes

AF:

0.802

AC:

121837

AN:

151976

Hom.:

50045

Cov.:

show subpopulations

Gnomad AFR

AF:

0.600

Gnomad AMI

AF:

0.849

Gnomad AMR

AF:

0.844

Gnomad ASJ

AF:

0.832

Gnomad EAS

AF:

0.996

Gnomad SAS

AF:

0.895

Gnomad FIN

AF:

0.828

Gnomad MID

AF:

0.810

Gnomad NFE

AF:

0.886

Gnomad OTH

AF:

0.833

GnomAD4 exome

AF:

0.863

AC:

214

AN:

248

Hom.:

Cov.:

AF XY:

0.882

AC XY:

127

AN XY:

144

show subpopulations

African (AFR)

AF:

0.400

AC:

AN:

American (AMR)

AF:

0.250

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.833

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

0.950

AC:

AN:

European-Finnish (FIN)

AF:

0.833

AC:

AN:

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.885

AC:

131

AN:

148

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.801

AC:

121900

AN:

152094

Hom.:

50065

Cov.:

AF XY:

0.803

AC XY:

59744

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.600

AC:

24848

AN:

41442

American (AMR)

AF:

0.845

AC:

12910

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.832

AC:

2888

AN:

3470

East Asian (EAS)

AF:

0.996

AC:

5150

AN:

5170

South Asian (SAS)

AF:

0.895

AC:

4316

AN:

4824

European-Finnish (FIN)

AF:

0.828

AC:

8760

AN:

10576

Middle Eastern (MID)

AF:

0.803

AC:

236

AN:

294

European-Non Finnish (NFE)

AF:

0.886

AC:

60255

AN:

68012

Other (OTH)

AF:

0.834

AC:

1764

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1107

2213

3320

4426

5533

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

866

1732

2598

3464

4330

<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:

0.864

Hom.:

249108

Bravo

AF:

0.796

Asia WGS

AF:

0.921

AC:

3198

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.50

(source)

DANN

Benign

0.18

PhyloP100

-2.9

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over