17-34256113-G-C

Variant names:

• chr17-34256113-G-C
• rs2857657
• NM_002982.4:c.77-109G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002982.4(CCL2):​c.77-109G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.838 in 715,820 control chromosomes in the GnomAD database, including 252,363 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.86 (56729 hom., cov: 33)
  • Exomes 𝑓: 0.83 (195634 hom.)
• Consequence: CCL2 NM_002982.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0420
• Publications: 27 publications found

Genes affected

CCL2 (HGNC:10618): (C-C motif chemokine ligand 2) This gene is one of several cytokine genes clustered on the q-arm of chromosome 17. Chemokines are a superfamily of secreted proteins involved in immunoregulatory and inflammatory processes. The superfamily is divided into four subfamilies based on the arrangement of N-terminal cysteine residues of the mature peptide. This chemokine is a member of the CC subfamily which is characterized by two adjacent cysteine residues. This cytokine displays chemotactic activity for monocytes and basophils but not for neutrophils or eosinophils. It has been implicated in the pathogenesis of diseases characterized by monocytic infiltrates, like psoriasis, rheumatoid arthritis and atherosclerosis. It binds to chemokine receptors CCR2 and CCR4. Elevated expression of the encoded protein is associated with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. [provided by RefSeq, Aug 2020]

CCL2 Gene-Disease associations (from GenCC):

• neural tube defects, susceptibility to

  Inheritance: AD Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002982.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCL2	NM_002982.4	MANE Select	c.77-109G>C		intron	N/A	NP_002973.1	P13500

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCL2	ENST00000225831.4	TSL:1 MANE Select	c.77-109G>C		intron	N/A	ENSP00000225831.4	P13500
	CCL2	ENST00000580907.6	TSL:2	c.77-109G>C		intron	N/A	ENSP00000462156.1	J3KRT7
	CCL2	ENST00000624362.2	TSL:6	n.829G>C		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.860 AC: 130873 AN: 152130 Hom.: 56664 Cov.: 33

Gnomad AFR AF: 0.956

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.869

Gnomad ASJ AF: 0.842

Gnomad EAS AF: 0.919

Gnomad SAS AF: 0.916

Gnomad FIN AF: 0.836

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.802

Gnomad OTH AF: 0.839

GnomAD4 exome AF: 0.831 AC: 468539 AN: 563572 Hom.: 195634 Cov.: 7 AF XY: 0.834 AC XY: 249084 AN XY: 298758

African (AFR) AF: 0.956 AC: 14525 AN: 15194

American (AMR) AF: 0.896 AC: 27813 AN: 31042

Ashkenazi Jewish (ASJ) AF: 0.834 AC: 13155 AN: 15776

East Asian (EAS) AF: 0.930 AC: 32463 AN: 34910

South Asian (SAS) AF: 0.912 AC: 48327 AN: 52974

European-Finnish (FIN) AF: 0.834 AC: 32393 AN: 38842

Middle Eastern (MID) AF: 0.833 AC: 3140 AN: 3770

European-Non Finnish (NFE) AF: 0.797 AC: 271844 AN: 341024

Other (OTH) AF: 0.828 AC: 24879 AN: 30040

GnomAD4 genome AF: 0.860 AC: 131000 AN: 152248 Hom.: 56729 Cov.: 33 AF XY: 0.865 AC XY: 64340 AN XY: 74422

African (AFR) AF: 0.956 AC: 39741 AN: 41560

American (AMR) AF: 0.869 AC: 13295 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.842 AC: 2924 AN: 3472

East Asian (EAS) AF: 0.919 AC: 4754 AN: 5174

South Asian (SAS) AF: 0.916 AC: 4422 AN: 4830

European-Finnish (FIN) AF: 0.836 AC: 8855 AN: 10598

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.802 AC: 54541 AN: 68002

Other (OTH) AF: 0.839 AC: 1774 AN: 2114

Alfa AF: 0.842 Hom.: 6690

Bravo AF: 0.864

Asia WGS AF: 0.926 AC: 3220 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.6
DANN	Benign	0.71
PhyloP100		0.042
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2857657; hg19: chr17-32583132;