4-74098622-A-C

Variant names:

• chr4-74098622-A-C
• NM_002089.4:c.287T>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002089.4(CXCL2):​c.287T>G​(p.Ile96Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CXCL2 NM_002089.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.73

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCL2	NM_002089.4	c.287T>G	p.Ile96Ser	missense_variant	Exon 3 of 4	ENST00000508487.3	NP_002080.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCL2	ENST00000508487.3	c.287T>G	p.Ile96Ser	missense_variant	Exon 3 of 4	1	NM_002089.4	ENSP00000427279.1
CXCL2	ENST00000296031.4	n.460T>G		non_coding_transcript_exon_variant	Exon 2 of 3	1
CXCL2	ENST00000510048.1	n.477T>G		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 05, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.287T>G (p.I96S) alteration is located in exon 3 (coding exon 3) of the CXCL2 gene. This alteration results from a T to G substitution at nucleotide position 287, causing the isoleucine (I) at amino acid position 96 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	T
Eigen	Benign	0.12
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.56	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.0057	T
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.3	M
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Benign	0.083
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.95	P
Vest4		0.53
MutPred		0.66		Loss of catalytic residue at L101 (P = 0.0469);
MVP		0.36
MPC		1.2
ClinPred		0.98	D
GERP RS		3.4
Varity_R		0.71
gMVP		0.39

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-74964339;