4-153704799-C-T

Variant names:

• chr4-153704799-C-T
• rs5743704
• NM_001318789.2:c.1892C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001318789.2(TLR2):​c.1892C>T​(p.Pro631Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TLR2 NM_001318789.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.09
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR2	NM_001318789.2	c.1892C>T	p.Pro631Leu	missense_variant	Exon 3 of 3	ENST00000642700.2	NP_001305718.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR2	ENST00000642700.2	c.1892C>T	p.Pro631Leu	missense_variant	Exon 3 of 3		NM_001318789.2	ENSP00000494425.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Uncertain	0.051	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	T;T;T;T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.99	.;.;.;D
M_CAP	Benign	0.045	D
MetaRNN	Uncertain	0.56	D;D;D;D
MetaSVM	Benign	-0.63	T
MutationAssessor	Pathogenic	3.3	M;M;M;M
PhyloP100		4.1
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-5.5	.;.;.;D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0010	.;.;.;D
Sift4G	Uncertain	0.0020	.;.;.;D
Polyphen		0.94	P;P;P;P
Vest4		0.41
MutPred		0.35		Loss of glycosylation at P631 (P = 0.0104);Loss of glycosylation at P631 (P = 0.0104);Loss of glycosylation at P631 (P = 0.0104);Loss of glycosylation at P631 (P = 0.0104);
MVP		0.82
MPC		0.41
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.47
gMVP		0.68
Mutation Taster		=81/19	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs5743704; hg19: chr4-154625951;