3-46358414-C-A

Position:

• chr3-46358414-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_001123396.4(CCR2):​c.887C>A​(p.Thr296Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCR2 NM_001123396.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 1.24

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 3-46358414-C-A is Pathogenic according to our data. Variant chr3-46358414-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 3061927.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	c.887C>A	p.Thr296Asn	missense_variant	2/2	ENST00000445132.3
CCR2	NM_001123041.3	c.887C>A	p.Thr296Asn	missense_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCR2	ENST00000445132.3	c.887C>A	p.Thr296Asn	missense_variant	2/2	1	NM_001123396.4	P2
CCR2	ENST00000400888.2	c.887C>A	p.Thr296Asn	missense_variant	1/2	1		A2
CCR2	ENST00000465202.1	n.612C>A		non_coding_transcript_exon_variant	2/2	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

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	0.65
BayesDel_addAF	Benign	-0.085	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	21
DANN	Uncertain	0.99
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Benign	0.69	D
LIST_S2	Uncertain	0.89	D;D;.
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.74	D;D;D
MetaSVM	Benign	-0.35	T
MutationAssessor	Pathogenic	3.9	H;H;H
MutationTaster	Benign	0.71	N;N;N
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-3.6	D;D;D
REVEL	Benign	0.14
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.0080	D;D;D
Polyphen		1.0	.;D;D
Vest4		0.55
MutPred		0.60		Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP		0.71
MPC		0.72
ClinPred		0.99	D
GERP RS		4.1
Varity_R		0.95
gMVP		0.52

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-46399905;