chr17-34256250-T-C

Variant names:

• chr17-34256250-T-C
• rs4586
• NM_002982.4:c.105T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_002982.4(CCL2):​c.105T>C​(p.Cys35Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 1,609,614 control chromosomes in the GnomAD database, including 133,317 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.47 (18471 hom., cov: 32)
  • Exomes 𝑓: 0.39 (114846 hom.)
• Consequence: CCL2 NM_002982.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.394
• Publications: 118 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 17-34256250-T-C is Benign according to our data. Variant chr17-34256250-T-C is described in ClinVar as Benign. ClinVar VariationId is 3059105.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.394 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.658 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.105T>C	p.Cys35Cys	synonymous	Exon 2 of 3	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.105T>C	p.Cys35Cys	synonymous	Exon 2 of 3	ENSP00000225831.4	P13500
	CCL2	ENST00000580907.6	TSL:2	c.105T>C	p.Cys35Cys	synonymous	Exon 2 of 2	ENSP00000462156.1	J3KRT7
	CCL2	ENST00000624362.2	TSL:6	n.966T>C		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.474 AC: 72025 AN: 151884 Hom.: 18430 Cov.: 32

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.539

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.458

GnomAD2 exomes AF: 0.444 AC: 111431 AN: 250930 AF XY: 0.431

Gnomad AFR exome AF: 0.676

Gnomad AMR exome AF: 0.604

Gnomad ASJ exome AF: 0.353

Gnomad EAS exome AF: 0.554

Gnomad FIN exome AF: 0.414

Gnomad NFE exome AF: 0.358

Gnomad OTH exome AF: 0.403

GnomAD4 exome AF: 0.388 AC: 565637 AN: 1457608 Hom.: 114846 Cov.: 31 AF XY: 0.388 AC XY: 281380 AN XY: 725212

African (AFR) AF: 0.676 AC: 22559 AN: 33388

American (AMR) AF: 0.597 AC: 26654 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 9229 AN: 26100

East Asian (EAS) AF: 0.611 AC: 24224 AN: 39646

South Asian (SAS) AF: 0.453 AC: 38973 AN: 86074

European-Finnish (FIN) AF: 0.408 AC: 21783 AN: 53364

Middle Eastern (MID) AF: 0.427 AC: 2458 AN: 5754

European-Non Finnish (NFE) AF: 0.357 AC: 395473 AN: 1108390

Other (OTH) AF: 0.403 AC: 24284 AN: 60218

GnomAD4 genome AF: 0.474 AC: 72121 AN: 152006 Hom.: 18471 Cov.: 32 AF XY: 0.478 AC XY: 35499 AN XY: 74310

African (AFR) AF: 0.665 AC: 27578 AN: 41470

American (AMR) AF: 0.540 AC: 8259 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1229 AN: 3464

East Asian (EAS) AF: 0.557 AC: 2862 AN: 5136

South Asian (SAS) AF: 0.454 AC: 2186 AN: 4810

European-Finnish (FIN) AF: 0.409 AC: 4322 AN: 10558

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.359 AC: 24390 AN: 67958

Other (OTH) AF: 0.455 AC: 960 AN: 2110

Alfa AF: 0.396 Hom.: 37062

Bravo AF: 0.493

Asia WGS AF: 0.508 AC: 1769 AN: 3478

EpiCase AF: 0.357

EpiControl AF: 0.359

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	CCL2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.6
DANN	Benign	0.41
PhyloP100		0.39
Mutation Taster		=98/2	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: rs4586; hg19: chr17-32583269; COSMIC: COSV56773536; COSMIC: COSV56773536;