Genetic Variant NM_002089.4:c.22G>T (chr4-74099099-C-A) – 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.22G>T(p.Ala8Ser) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A8T) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CXCL2
NM_002089.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.70

Publications

1 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=0.060518533).

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.22G>T	p.Ala8Ser	missense	Exon 1 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.22G>T	p.Ala8Ser	missense	Exon 1 of 4	ENSP00000427279.1	P19875
CXCL2	ENST00000296031.4	TSL:1	n.97G>T		non_coding_transcript_exon	Exon 1 of 3
CXCL2	ENST00000906203.1		c.22G>T	p.Ala8Ser	missense	Exon 1 of 4	ENSP00000576262.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

93368

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1343898

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

662276

African (AFR)

AF:

0.00

AC:

AN:

27094

American (AMR)

AF:

0.00

AC:

AN:

28928

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23384

East Asian (EAS)

AF:

0.00

AC:

AN:

28852

South Asian (SAS)

AF:

0.00

AC:

AN:

73880

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44738

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4812

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1056578

Other (OTH)

AF:

0.00

AC:

AN:

55632

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.087

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.099

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.67

M_CAP

Benign

0.0038

MetaRNN

Benign

0.061

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PhyloP100

-1.7

PrimateAI

Uncertain

0.69

PROVEAN

Benign

0.020

REVEL

Benign

0.030

Sift

Benign

0.23

Sift4G

Benign

0.39

Polyphen

0.088

Vest4

0.11

MutPred

0.11

Loss of glycosylation at P10 (P = 0.0203)

MVP

0.061

MPC

0.36

ClinPred

0.088

GERP RS

-0.75

PromoterAI

-0.042

Neutral

(source)

Varity_R

0.058

gMVP

0.066

Mutation Taster

=100/0

polymorphism

(source)

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

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