chr17-34255978-ACAGCTCCTCCTTCT-A

Variant names:

• chr17-34255978-ACAGCTCCTCCTTCT-A
• rs3917887
• NM_002982.4:c.77-242_77-229delAGCTCCTCCTTCTC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_002982.4(CCL2):​c.77-242_77-229delAGCTCCTCCTTCTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 451,188 control chromosomes in the GnomAD database, including 26,054 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.33 (8997 hom., cov: 0)
  • Exomes 𝑓: 0.33 (17057 hom.)
• Consequence: CCL2 NM_002982.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.371
• Publications: 23 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 -8 ACMG points.

• 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.77-242_77-229delAGCTCCTCCTTCTC		intron_variant	Intron 1 of 2	ENST00000225831.4	NP_002973.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCL2	ENST00000225831.4	c.77-242_77-229delAGCTCCTCCTTCTC		intron_variant	Intron 1 of 2	1	NM_002982.4	ENSP00000225831.4
CCL2	ENST00000624362.2	n.696_709delAGCTCCTCCTTCTC		non_coding_transcript_exon_variant	Exon 1 of 1	6
CCL2	ENST00000580907.6	c.77-242_77-229delAGCTCCTCCTTCTC		intron_variant	Intron 1 of 1	2		ENSP00000462156.1

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50725 AN: 151932 Hom.: 8976 Cov.: 0

Gnomad AFR AF: 0.366

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.320

GnomAD4 exome AF: 0.326 AC: 97486 AN: 299136 Hom.: 17057 AF XY: 0.325 AC XY: 50575 AN XY: 155780

African (AFR) AF: 0.380 AC: 3429 AN: 9024

American (AMR) AF: 0.498 AC: 6108 AN: 12266

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 2826 AN: 9834

East Asian (EAS) AF: 0.624 AC: 13917 AN: 22298

South Asian (SAS) AF: 0.340 AC: 8820 AN: 25906

European-Finnish (FIN) AF: 0.348 AC: 6440 AN: 18528

Middle Eastern (MID) AF: 0.260 AC: 359 AN: 1382

European-Non Finnish (NFE) AF: 0.274 AC: 49869 AN: 181892

Other (OTH) AF: 0.318 AC: 5718 AN: 18006

GnomAD4 genome AF: 0.334 AC: 50790 AN: 152052 Hom.: 8997 Cov.: 0 AF XY: 0.340 AC XY: 25300 AN XY: 74324

African (AFR) AF: 0.366 AC: 15192 AN: 41474

American (AMR) AF: 0.450 AC: 6874 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 977 AN: 3468

East Asian (EAS) AF: 0.555 AC: 2857 AN: 5150

South Asian (SAS) AF: 0.344 AC: 1657 AN: 4818

European-Finnish (FIN) AF: 0.343 AC: 3633 AN: 10592

Middle Eastern (MID) AF: 0.298 AC: 87 AN: 292

European-Non Finnish (NFE) AF: 0.275 AC: 18710 AN: 67952

Other (OTH) AF: 0.319 AC: 675 AN: 2116

Alfa AF: 0.298 Hom.: 819

Bravo AF: 0.344

Asia WGS AF: 0.450 AC: 1565 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.37
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs3917887; hg19: chr17-32582997; COSMIC: COSV56773479; COSMIC: COSV56773479;