Genetic Variant CXCL2:p.Gln50Arg (chr4-74098874-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002089.4(CXCL2):c.149A>G(p.Gln50Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q50L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

CXCL2
NM_002089.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.635

Publications

2 publications found

Variant links:

Genes affected

CXCL2 (HGNC:4603): (C-X-C motif chemokine ligand 2) This antimicrobial gene is part of a chemokine superfamily that encodes secreted proteins involved in immunoregulatory and inflammatory processes. The superfamily is divided into four subfamilies based on the arrangement of the N-terminal cysteine residues of the mature peptide. This chemokine, a member of the CXC subfamily, is expressed at sites of inflammation and may suppress hematopoietic progenitor cell proliferation. [provided by RefSeq, Sep 2014]

CXCL2 links:

ENSG00000289241 (HGNC:):

ENSG00000289241 links:

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ACMG classification

Classification was made for transcript

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 (MetaRNN=0.055254698).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002089.4. 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
	CXCL2	NM_002089.4	MANE Select	c.149A>G	p.Gln50Arg	missense	Exon 2 of 4	NP_002080.1	P19875

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CXCL2	ENST00000508487.3	TSL:1 MANE Select	c.149A>G	p.Gln50Arg	missense	Exon 2 of 4	ENSP00000427279.1	P19875
CXCL2	ENST00000296031.4	TSL:1	n.322A>G		non_coding_transcript_exon	Exon 1 of 3
CXCL2	ENST00000906203.1		c.164A>G	p.Gln55Arg	missense	Exon 2 of 4	ENSP00000576262.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251416

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.76

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.11

Eigen

Benign

-0.95

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.070

LIST_S2

Benign

0.46

M_CAP

Benign

0.0022

MetaRNN

Benign

0.055

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.8

PhyloP100

0.64

PrimateAI

Benign

0.35

PROVEAN

Benign

-2.1

REVEL

Benign

0.028

Sift

Benign

0.30

Sift4G

Benign

0.41

Polyphen

0.0030

Vest4

0.25

MutPred

0.25

Gain of MoRF binding (P = 0.0249)

MVP

0.088

MPC

0.33

ClinPred

0.046

GERP RS

-0.62

PromoterAI

0.0093

Neutral

(source)

Varity_R

0.098

gMVP

0.046

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over