3-46358308-A-G

Position:

• chr3-46358308-A-G

Variant summary

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

The NM_001123396.4(CCR2):​c.781A>G​(p.Ile261Val) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCR2 NM_001123396.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.339

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]

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=0.15984362).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCR2	NM_001123396.4	c.781A>G	p.Ile261Val	missense_variant	2/2	ENST00000445132.3
CCR2	NM_001123041.3	c.781A>G	p.Ile261Val	missense_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCR2	ENST00000445132.3	c.781A>G	p.Ile261Val	missense_variant	2/2	1	NM_001123396.4	P2
CCR2	ENST00000400888.2	c.781A>G	p.Ile261Val	missense_variant	1/2	1		A2
CCR2	ENST00000465202.1	n.506A>G		non_coding_transcript_exon_variant	2/2	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

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

Jul 20, 2021

The c.781A>G (p.I261V) alteration is located in exon 2 (coding exon 1) of the CCR2 gene. This alteration results from a A to G substitution at nucleotide position 781, causing the isoleucine (I) at amino acid position 261 to be replaced by a valine (V). 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	0.072
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	0.63
DANN	Benign	0.84
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.81	T;D;.
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.3	L;L;L
MutationTaster	Benign	0.98	D;D;D
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.85	N;N;N
REVEL	Benign	0.10
Sift	Benign	0.073	T;T;T
Sift4G	Benign	0.54	T;T;T
Polyphen		0.24	.;B;B
Vest4		0.12
MutPred		0.60		Loss of catalytic residue at I261 (P = 0.3866);Loss of catalytic residue at I261 (P = 0.3866);Loss of catalytic residue at I261 (P = 0.3866);
MVP		0.58
MPC		0.23
ClinPred		0.15	T
GERP RS		-1.7
Varity_R		0.067
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-46399799;