3-46357586-T-TAC

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_Strong PM2 PP5

The NM_001123396.4(CCR2):c.59_60insAC(p.Thr21ProfsTer18) variant causes a frameshift 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 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 1.10

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 Likely_pathogenic. Variant got 7 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 5 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 3-46357586-T-TAC is Pathogenic according to our data. Variant chr3-46357586-T-TAC is described in ClinVar as [Pathogenic]. Clinvar id is 3061928.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.59_60insAC	p.Thr21ProfsTer18	frameshift_variant	2/2	ENST00000445132.3
CCR2	NM_001123041.3	c.59_60insAC	p.Thr21ProfsTer18	frameshift_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCR2	ENST00000445132.3	c.59_60insAC	p.Thr21ProfsTer18	frameshift_variant	2/2	1	NM_001123396.4	P2
CCR2	ENST00000400888.2	c.59_60insAC	p.Thr21ProfsTer18	frameshift_variant	1/2	1		A2
CCR2	ENST00000421659.1	c.59_60insAC	p.Thr21ProfsTer18	frameshift_variant	3/3	4
CCR2	ENST00000465202.1	n.315-531_315-530insAC		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1268159081; hg19: chr3-46399077;