Variant 3-46357709-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5

The NM_001123396.4(CCR2):c.182T>G(p.Met61Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CCR2
NM_001123396.4 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 1.21

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 3-46357709-T-G is Pathogenic according to our data. Variant chr3-46357709-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 3061926.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCR2	NM_001123396.4 linkuse as main transcript	c.182T>G	p.Met61Arg	missense_variant	2/2	ENST00000445132.3
CCR2	NM_001123041.3 linkuse as main transcript	c.182T>G	p.Met61Arg	missense_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCR2	ENST00000445132.3 linkuse as main transcript	c.182T>G	p.Met61Arg	missense_variant	2/2	1	NM_001123396.4	P2	P41597-2
CCR2	ENST00000400888.2 linkuse as main transcript	c.182T>G	p.Met61Arg	missense_variant	1/2	1		A2	P41597-1
CCR2	ENST00000421659.1 linkuse as main transcript	c.182T>G	p.Met61Arg	missense_variant	3/3	4
CCR2	ENST00000465202.1 linkuse as main transcript	n.315-408T>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251334

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135850

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Cystic disease of lung

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Mar 12, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.68

BayesDel_addAF

Benign

-0.064

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

0.98

Eigen

Benign

0.023

Eigen_PC

Benign

-0.056

FATHMM_MKL

Benign

0.11

LIST_S2

Uncertain

0.92

D;D;D;.

M_CAP

Benign

0.018

MetaRNN

Uncertain

0.69

D;D;D;D

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.8

M;M;.;M

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-2.9

D;D;D;D

REVEL

Benign

0.19

Sift

Uncertain

0.0010

D;D;D;D

Sift4G

Benign

0.086

T;T;T;T

Polyphen

0.85

.;P;.;P

Vest4

0.31

MutPred

0.91

Gain of methylation at M61 (P = 0.0134);Gain of methylation at M61 (P = 0.0134);Gain of methylation at M61 (P = 0.0134);Gain of methylation at M61 (P = 0.0134);

MVP

0.69

MPC

0.66

ClinPred

0.48

GERP RS

1.9

Varity_R

0.82

gMVP

0.65

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over