Variant 3-46358570-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001123396.4(CCR2):c.1043C>T(p.Thr348Met) variant causes a missense change. The variant allele was found at a frequency of 0.000207 in 1,603,228 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. T348T) has been classified as Benign.

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00022 ( 1 hom. )

Consequence

CCR2
NM_001123396.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.60

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCR2	NM_001123396.4 linkuse as main transcript	c.1043C>T	p.Thr348Met	missense_variant	2/2	ENST00000445132.3
CCR2	NM_001123041.3 linkuse as main transcript	c.941+102C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCR2	ENST00000445132.3 linkuse as main transcript	c.1043C>T	p.Thr348Met	missense_variant	2/2	1	NM_001123396.4	P2	P41597-2
CCR2	ENST00000400888.2 linkuse as main transcript	c.941+102C>T		intron_variant		1		A2	P41597-1
CCR2	ENST00000465202.1 linkuse as main transcript	n.768C>T		non_coding_transcript_exon_variant	2/2	5

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000172

AC:

AN:

227032

Hom.:

AF XY:

0.000179

AC XY:

AN XY:

122766

show subpopulations

Gnomad AFR exome

AF:

0.0000744

Gnomad AMR exome

AF:

0.0000943

Gnomad ASJ exome

AF:

0.000107

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000349

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000318

Gnomad OTH exome

AF:

0.000176

GnomAD4 exome

AF:

0.000216

AC:

313

AN:

1450946

Hom.:

Cov.:

AF XY:

0.000211

AC XY:

152

AN XY:

720570

show subpopulations

Gnomad4 AFR exome

AF:

0.0000900

Gnomad4 AMR exome

AF:

0.0000705

Gnomad4 ASJ exome

AF:

0.0000389

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000589

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000261

Gnomad4 OTH exome

AF:

0.000200

GnomAD4 genome

AF:

0.000125

AC:

AN:

152282

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000148

Hom.:

Bravo

AF:

0.000166

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000183

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Susceptibility to HIV infection

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago

Mar 30, 2021

CCR2 NM_001123396.2 exon 2 p.Thr348Met (c.1043C>T): This variant has been reported in the literature in at least 1 individual with very early onset inflammatory bowel disease (VEO-IBD) (Kelsen 2015 PMID:26193622). This variant is present in 0.02% (34/115940) of European alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/3-46400061-C-T). Evolutionary conservation and computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.24

Cadd

Uncertain

Dann

Uncertain

1.0

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.94

M_CAP

Uncertain

0.12

MetaRNN

Uncertain

0.44

MetaSVM

Uncertain

0.32

MutationTaster

Benign

1.0

D;D;N

PROVEAN

Uncertain

-3.0

REVEL

Uncertain

0.44

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0020

Vest4

0.37

MVP

0.89

ClinPred

0.12

GERP RS

4.9

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