Genetic Variant NM_001123396.4:c.182T>G (chr3-46357709-T-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 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

Publications

1 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 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 VariationId is 3061926.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCR2	NM_001123396.4 link	c.182T>G	p.Met61Arg	missense_variant	Exon 2 of 2	ENST00000445132.3	NP_001116868.1	P41597-2A0A024R2Q0
CCR2	NM_001123041.3 link	c.182T>G	p.Met61Arg	missense_variant	Exon 2 of 3		NP_001116513.2	P41597-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CCR2	ENST00000445132.3 link	c.182T>G	p.Met61Arg	missense_variant	Exon 2 of 2	1	NM_001123396.4	ENSP00000399285.2	P41597-2
CCR2	ENST00000400888.2 link	c.182T>G	p.Met61Arg	missense_variant	Exon 1 of 2	1		ENSP00000383681.2	P41597-1
CCR2	ENST00000421659.1 link	c.182T>G	p.Met61Arg	missense_variant	Exon 3 of 3	4		ENSP00000396736.1	E9PH76
CCR2	ENST00000465202.1 link	n.315-408T>G		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251334

AF XY:

0.00000736

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 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

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111998

Other (OTH)

AF:

0.0000166

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Mar 12, 2024

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

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

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.30

.;T;.;T

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

PhyloP100

1.2

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

PromoterAI

-0.018

Neutral

(source)

Varity_R

0.82

gMVP

0.65

Mutation Taster

=72/28

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over