4-153703386-A-G

Variant names:

• chr4-153703386-A-G
• NM_001318789.2:c.479A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001318789.2(TLR2):​c.479A>G​(p.Asp160Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: TLR2 NM_001318789.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.05
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18993506).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR2	NM_001318789.2	MANE Select	c.479A>G	p.Asp160Gly	missense	Exon 3 of 3	NP_001305718.1	O60603
	TLR2	NM_001318787.2		c.479A>G	p.Asp160Gly	missense	Exon 4 of 4	NP_001305716.1	A0A0S2Z4S4
	TLR2	NM_001318790.2		c.479A>G	p.Asp160Gly	missense	Exon 3 of 3	NP_001305719.1	A0A0S2Z4S4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR2	ENST00000642700.2	MANE Select	c.479A>G	p.Asp160Gly	missense	Exon 3 of 3	ENSP00000494425.1	O60603
	TLR2	ENST00000260010.7	TSL:6	c.479A>G	p.Asp160Gly	missense	Exon 3 of 3	ENSP00000260010.6	O60603
	TLR2	ENST00000642580.1		c.479A>G	p.Asp160Gly	missense	Exon 3 of 3	ENSP00000495339.1	O60603

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	8.4
DANN	Benign	0.69
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.13	N
LIST_S2	Uncertain	0.88	D
M_CAP	Uncertain	0.098	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.55	T
MutationAssessor	Benign	0.76	N
PhyloP100		1.0
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.27
Sift	Benign	0.25	T
Sift4G	Benign	0.42	T
Polyphen		0.016	B
Vest4		0.12
MutPred		0.58		Loss of ubiquitination at K164 (P = 0.0327)
MVP		0.99
MPC		0.12
ClinPred		0.21	T
GERP RS		4.3
PromoterAI		-0.0013	Neutral
Varity_R		0.25
gMVP		0.40
Mutation Taster		=79/21	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

hg19: chr4-154624538;