NM_002982.4:c.*65C>T

Variant names:

• chr17-34256892-C-T
• rs13900
• NM_002982.4:c.*65C>T

Variant summary

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

The NM_002982.4(CCL2):​c.*65C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 923,064 control chromosomes in the GnomAD database, including 45,576 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 0.29 (6917 hom., cov: 32)
  • Exomes 𝑓: 0.30 (38659 hom.)
• Consequence: CCL2 NM_002982.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.224
• Publications: 57 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCL2	NM_002982.4	c.*65C>T		3_prime_UTR_variant	Exon 3 of 3	ENST00000225831.4	NP_002973.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCL2	ENST00000225831.4	c.*65C>T		3_prime_UTR_variant	Exon 3 of 3	1	NM_002982.4	ENSP00000225831.4
CCL2	ENST00000624362.2	n.1608C>T		non_coding_transcript_exon_variant	Exon 1 of 1	6
CCL2	ENST00000580907.6	c.*549C>T		3_prime_UTR_variant	Exon 2 of 2	2		ENSP00000462156.1

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43568 AN: 151918 Hom.: 6905 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.285

GnomAD4 exome AF: 0.298 AC: 229448 AN: 771026 Hom.: 38659 Cov.: 10 AF XY: 0.298 AC XY: 119827 AN XY: 402548

African (AFR) AF: 0.191 AC: 3682 AN: 19294

American (AMR) AF: 0.512 AC: 16349 AN: 31906

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 5496 AN: 19542

East Asian (EAS) AF: 0.619 AC: 21702 AN: 35060

South Asian (SAS) AF: 0.334 AC: 21294 AN: 63754

European-Finnish (FIN) AF: 0.343 AC: 17258 AN: 50330

Middle Eastern (MID) AF: 0.281 AC: 1207 AN: 4292

European-Non Finnish (NFE) AF: 0.258 AC: 131757 AN: 509932

Other (OTH) AF: 0.290 AC: 10703 AN: 36916

GnomAD4 genome AF: 0.287 AC: 43608 AN: 152038 Hom.: 6917 Cov.: 32 AF XY: 0.296 AC XY: 21971 AN XY: 74310

African (AFR) AF: 0.202 AC: 8389 AN: 41448

American (AMR) AF: 0.431 AC: 6582 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 979 AN: 3470

East Asian (EAS) AF: 0.555 AC: 2870 AN: 5170

South Asian (SAS) AF: 0.343 AC: 1652 AN: 4814

European-Finnish (FIN) AF: 0.344 AC: 3635 AN: 10566

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.275 AC: 18685 AN: 67982

Other (OTH) AF: 0.284 AC: 600 AN: 2110

Alfa AF: 0.274 Hom.: 7358

Bravo AF: 0.290

Asia WGS AF: 0.440 AC: 1529 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.8
DANN	Benign	0.63
PhyloP100		0.22
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: rs13900; hg19: chr17-32583911; COSMIC: COSV56773543; COSMIC: COSV56773543;