Genetic Variant CCR2:p.Pro214_Leu215del (chr3-46358163-CCTGCCG-C) – ACMG Classification: Uncertain_significance (5 pts)

Variant summary

Our verdict is The variant received 5 classification points (ACMG Germline Pathogenicity v2019). PM2PM4PP5

The NM_001123396.4(CCR2):c.641_646delCGCTGC (p.Pro214_Leu215del) variant causes a disruptive inframe deletion change. The variant results in an in-frame change. Note: allele frequency estimates from gnomAD may be inaccurate for this variant type (MNP or indel longer than 3 bp) due to technology limitations. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. The affected nucleotide is highly conserved across species (PhyloP 100-way vertebrate score: 7.92). Variant has been reported in ClinVar as Pathogenic/Likely Pathogenic (no review stars).

Frequency

Genomes: not found (cov: 32)

Consequence

CCR2
NM_001123396.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 7.92

Publications

0 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:

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new If you want to explore the variant's impact on the transcript NM_001123396.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 5 points.

PM2

Absent from gnomAD (AR/unknown gene) — PM2; Absent from gnomAD at well-covered site (MOI: AR) (threshold 0.001) — PM2 moderate.

PM4

In-frame indel in non-repetitive region — protein length change (PM4); In-frame indel in non-repetitive region — protein length change (2 AA).

PP5

ClinVar 0-star pathogenic — supporting (PP5); ClinVar germline classification: Pathogenic/Likely Pathogenic, 0 star(s).

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_001123396.4. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCR2	NM_001123396.4	MANE Select	c.641_646delCGCTGC	p.Pro214_Leu215del	disruptive_inframe_deletion	Exon 2 of 2	NP_001116868.1	P41597-2
	CCR2	NM_001123041.3		c.641_646delCGCTGC	p.Pro214_Leu215del	disruptive_inframe_deletion	Exon 2 of 3	NP_001116513.2	P41597-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCR2	ENST00000445132.3	TSL:1 MANE Select	c.641_646delCGCTGC	p.Pro214_Leu215del	disruptive_inframe_deletion	Exon 2 of 2	ENSP00000399285.2	P41597-2
CCR2	ENST00000400888.2	TSL:1	c.641_646delCGCTGC	p.Pro214_Leu215del	disruptive_inframe_deletion	Exon 1 of 2	ENSP00000383681.2	P41597-1
CCR2	ENST00000908302.1		c.641_646delCGCTGC	p.Pro214_Leu215del	disruptive_inframe_deletion	Exon 2 of 2	ENSP00000578361.1	P41597-2

Frequencies

GnomAD3 genomes

Cov.:

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Pathogenic

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Cystic disease of lung (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

7.9

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over