17-34256308-A-T
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_002982.4(CCL2):c.163A>T(p.Thr55Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,556 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
CCL2
NM_002982.4 missense
NM_002982.4 missense
Scores
6
12
Clinical Significance
Conservation
PhyloP100: 2.49
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.28782398).
BS2
High AC in GnomAdExome4 at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CCL2 | NM_002982.4 | c.163A>T | p.Thr55Ser | missense_variant | 2/3 | ENST00000225831.4 | NP_002973.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CCL2 | ENST00000225831.4 | c.163A>T | p.Thr55Ser | missense_variant | 2/3 | 1 | NM_002982.4 | ENSP00000225831 | P1 | |
CCL2 | ENST00000580907.6 | c.163A>T | p.Thr55Ser | missense_variant | 2/2 | 2 | ENSP00000462156 | |||
CCL2 | ENST00000624362.2 | n.1024A>T | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152170Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251128Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135716
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GnomAD4 exome AF: 0.00000411 AC: 6AN: 1461386Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 726988
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152170Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74336
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 20, 2024 | The c.163A>T (p.T55S) alteration is located in exon 2 (coding exon 2) of the CCL2 gene. This alteration results from a A to T substitution at nucleotide position 163, causing the threonine (T) at amino acid position 55 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;N
PrimateAI
Uncertain
T
PROVEAN
Uncertain
.;D
REVEL
Benign
Sift
Uncertain
.;D
Sift4G
Benign
T;T
Polyphen
0.93
.;P
Vest4
MutPred
Gain of disorder (P = 0.0362);Gain of disorder (P = 0.0362);
MVP
MPC
1.1
ClinPred
D
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at