Genetic Variant CXCR2:c.-141+218delT (chr2-218125576-GT-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000453237.5(CXCR2):c.-141+218delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 150,788 control chromosomes in the GnomAD database, including 28,044 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.60 ( 28042 hom., cov: 0)

Exomes 𝑓: 0.38 ( 2 hom. )

Consequence

CXCR2
ENST00000453237.5 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.467

Publications

1 publications found

Variant links:

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: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.776 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
CXCR2	NM_001168298.2 link	c.-141+222delT	intron_variant	Intron 1 of 3	NP_001161770.1	P25025Q53PC4
CXCR2	XM_047444190.1 link	c.-89+222delT	intron_variant	Intron 1 of 2	XP_047300146.1
CXCR2	XM_047444187.1 link	c.-345delT	upstream_gene_variant		XP_047300143.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
CXCR2	ENST00000453237.5 link	c.-141+218delT	intron_variant	Intron 1 of 3	1	ENSP00000413686.1	C9JW47
CXCR2	ENST00000449014.5 link	c.-345delT	upstream_gene_variant		1	ENSP00000410506.1	Q6LCZ7
CXCR2	ENST00000415392.5 link	c.-274delT	upstream_gene_variant		5	ENSP00000392348.1	C9J2F9

Frequencies

GnomAD3 genomes

AF:

0.597

AC:

89881

AN:

150646

Hom.:

28009

Cov.:

show subpopulations

Gnomad AFR

AF:

0.783

Gnomad AMI

AF:

0.723

Gnomad AMR

AF:

0.563

Gnomad ASJ

AF:

0.651

Gnomad EAS

AF:

0.355

Gnomad SAS

AF:

0.591

Gnomad FIN

AF:

0.430

Gnomad MID

AF:

0.725

Gnomad NFE

AF:

0.530

Gnomad OTH

AF:

0.621

GnomAD4 exome

AF:

0.385

AC:

AN:

Hom.:

AF XY:

0.409

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.375

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.597

AC:

89952

AN:

150762

Hom.:

28042

Cov.:

AF XY:

0.592

AC XY:

43532

AN XY:

73594

show subpopulations

African (AFR)

AF:

0.783

AC:

32132

AN:

41032

American (AMR)

AF:

0.563

AC:

8542

AN:

15184

Ashkenazi Jewish (ASJ)

AF:

0.651

AC:

2241

AN:

3444

East Asian (EAS)

AF:

0.355

AC:

1822

AN:

5128

South Asian (SAS)

AF:

0.591

AC:

2800

AN:

4736

European-Finnish (FIN)

AF:

0.430

AC:

4464

AN:

10382

Middle Eastern (MID)

AF:

0.734

AC:

210

AN:

286

European-Non Finnish (NFE)

AF:

0.530

AC:

35793

AN:

67576

Other (OTH)

AF:

0.620

AC:

1296

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1726

3451

5177

6902

8628

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

728

1456

2184

2912

3640

<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:

0.157

Hom.:

551

Asia WGS

AF:

0.479

AC:

1665

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.47

Splicing

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

Publications

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2-218125576-GTT-GT

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