chr3-46357687-A-C

Position:

• chr3-46357687-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001123396.4(CCR2):​c.160A>C​(p.Ile54Leu) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCR2 NM_001123396.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.884

Genes affected

CCR2 (HGNC:1603): (C-C motif chemokine receptor 2) The protein encoded by this gene is a receptor for monocyte chemoattractant protein-1, a chemokine which specifically mediates monocyte chemotaxis. Monocyte chemoattractant protein-1 is involved in monocyte infiltration in inflammatory diseases such as rheumatoid arthritis as well as in the inflammatory response against tumors. The encoded protein mediates agonist-dependent calcium mobilization and inhibition of adenylyl cyclase. This protein can also be a coreceptor with CD4 for HIV-1 infection. This gene is located in the chemokine receptor gene cluster region of chromosome 3. [provided by RefSeq, Aug 2017]

CCR2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1653992).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCR2	NM_001123396.4	c.160A>C	p.Ile54Leu	missense_variant	2/2	ENST00000445132.3	NP_001116868.1
CCR2	NM_001123041.3	c.160A>C	p.Ile54Leu	missense_variant	2/3		NP_001116513.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCR2	ENST00000445132.3	c.160A>C	p.Ile54Leu	missense_variant	2/2	1	NM_001123396.4	ENSP00000399285.2
CCR2	ENST00000400888.2	c.160A>C	p.Ile54Leu	missense_variant	1/2	1		ENSP00000383681.2
CCR2	ENST00000421659.1	c.160A>C	p.Ile54Leu	missense_variant	3/3	4		ENSP00000396736.1
CCR2	ENST00000465202.1	n.315-430A>C		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 20, 2024

The c.160A>C (p.I54L) alteration is located in exon 2 (coding exon 1) of the CCR2 gene. This alteration results from a A to C substitution at nucleotide position 160, causing the isoleucine (I) at amino acid position 54 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	13
DANN	Benign	0.93
DEOGEN2	Benign	0.045	.;T;.;T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.61	T;T;T;.
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.17	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.86	L;L;.;L
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.3	N;N;N;N
REVEL	Benign	0.079
Sift	Benign	0.17	T;T;T;T
Sift4G	Benign	0.43	T;T;T;T
Polyphen		0.0010	.;B;.;B
Vest4		0.27
MutPred		0.54		Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);
MVP		0.36
MPC		0.20
ClinPred		0.86	D
GERP RS		-1.1
Varity_R		0.20
gMVP		0.27

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

Publications

LitVar

Other links and lift over

dbSNP: rs1254516472; hg19: chr3-46399178;