17-34255522-C-T

Variant names:

• chr17-34255522-C-T
• rs41507946
• NM_002982.4:c.76+97C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002982.4(CCL2):​c.76+97C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000436 in 916,608 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000044 (0 hom.)
• Consequence: CCL2 NM_002982.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.180
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCL2	NM_002982.4	MANE Select	c.76+97C>T		intron	N/A	NP_002973.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCL2	ENST00000225831.4	TSL:1 MANE Select	c.76+97C>T		intron	N/A	ENSP00000225831.4
	CCL2	ENST00000624362.2	TSL:6	n.238C>T		non_coding_transcript_exon	Exon 1 of 1
	CCL2	ENST00000580907.6	TSL:2	c.76+97C>T		intron	N/A	ENSP00000462156.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000436 AC: 4 AN: 916608 Hom.: 0 Cov.: 12 AF XY: 0.00000637 AC XY: 3 AN XY: 471074

African (AFR) AF: 0.00 AC: 0 AN: 21800

American (AMR) AF: 0.0000291 AC: 1 AN: 34380

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19678

East Asian (EAS) AF: 0.00 AC: 0 AN: 34916

South Asian (SAS) AF: 0.0000148 AC: 1 AN: 67602

European-Finnish (FIN) AF: 0.0000221 AC: 1 AN: 45216

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4546

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 646642

Other (OTH) AF: 0.0000239 AC: 1 AN: 41828

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	6.6
DANN	Benign	0.84
PhyloP100		-0.18
PromoterAI		-0.033	Neutral

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: rs41507946; hg19: chr17-32582541;