Genetic Variant CXCR2:c.-141+223_-141+224insT (chr2-218125582-G-GT) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The ENST00000453237.5(CXCR2):c.-141+223_-141+224insT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00089 ( 1 hom., cov: 0)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CXCR2
ENST00000453237.5 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.557

Publications

0 publications found

Variant links:

COSMIC-nc: COSV59281518

Genes affected

CXCR2 (HGNC:6027): (C-X-C motif chemokine receptor 2) The protein encoded by this gene is a member of the G-protein-coupled receptor family. This protein is a receptor for interleukin 8 (IL8). It binds to IL8 with high affinity, and transduces the signal through a G-protein activated second messenger system. This receptor also binds to chemokine (C-X-C motif) ligand 1 (CXCL1/MGSA), a protein with melanoma growth stimulating activity, and has been shown to be a major component required for serum-dependent melanoma cell growth. This receptor mediates neutrophil migration to sites of inflammation. The angiogenic effects of IL8 in intestinal microvascular endothelial cells are found to be mediated by this receptor. Knockout studies in mice suggested that this receptor controls the positioning of oligodendrocyte precursors in developing spinal cord by arresting their migration. This gene, IL8RA, a gene encoding another high affinity IL8 receptor, as well as IL8RBP, a pseudogene of IL8RB, form a gene cluster in a region mapped to chromosome 2q33-q36. Alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Nov 2009]

CXCR2 Gene-Disease associations (from GenCC):

WHIM syndrome 2
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
autosomal recessive severe congenital neutropenia due to CXCR2 deficiency
Inheritance: AR Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics

CXCR2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
CXCR2	NM_001168298.2 link	c.-141+234dupT	intron_variant	Intron 1 of 3	NP_001161770.1
CXCR2	XM_047444190.1 link	c.-89+234dupT	intron_variant	Intron 1 of 2	XP_047300146.1
CXCR2	XM_047444187.1 link	c.-340_-339insT	upstream_gene_variant		XP_047300143.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein
CXCR2	ENST00000453237.5 link	c.-141+223_-141+224insT	intron_variant	Intron 1 of 3	1	ENSP00000413686.1
CXCR2	ENST00000449014.5 link	c.-340_-339insT	upstream_gene_variant		1	ENSP00000410506.1
CXCR2	ENST00000415392.5 link	c.-269_-268insT	upstream_gene_variant		5	ENSP00000392348.1

Frequencies

GnomAD3 genomes

AF:

0.000865

AC:

128

AN:

148044

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000372

Gnomad AMI

AF:

0.00336

Gnomad AMR

AF:

0.00135

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000599

Gnomad SAS

AF:

0.000642

Gnomad FIN

AF:

0.00245

Gnomad MID

AF:

0.00654

Gnomad NFE

AF:

0.000794

Gnomad OTH

AF:

0.00247

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

GnomAD4 genome

AF:

0.000891

AC:

132

AN:

148144

Hom.:

Cov.:

AF XY:

0.000915

AC XY:

AN XY:

72156

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000470

AC:

AN:

40452

American (AMR)

AF:

0.00134

AC:

AN:

14872

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3418

East Asian (EAS)

AF:

0.000600

AC:

AN:

4996

South Asian (SAS)

AF:

0.000643

AC:

AN:

4664

European-Finnish (FIN)

AF:

0.00245

AC:

AN:

9790

Middle Eastern (MID)

AF:

0.00699

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.000794

AC:

AN:

66732

Other (OTH)

AF:

0.00245

AC:

AN:

2042

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000000000000366374), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000184

Hom.:

521

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.56

Splicing

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

Publications

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2-218125582-GTTT-GTTTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over