rs2230054

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001557.4(CXCR2):c.786C>T(p.Leu262Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 1,613,788 control chromosomes in the GnomAD database, including 196,054 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 22382 hom., cov: 31)

Exomes 𝑓: 0.48 ( 173672 hom. )

Consequence

CXCR2
NM_001557.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.953

Publications

59 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:

ENSG00000305582 (HGNC:):

ENSG00000305582 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 2-218135587-C-T is Benign according to our data. Variant chr2-218135587-C-T is described in ClinVar as Benign. ClinVar VariationId is 1164812.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.953 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCR2	NM_001557.4 link	c.786C>T	p.Leu262Leu	synonymous_variant	Exon 3 of 3	ENST00000318507.7	NP_001548.1	P25025Q53PC4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CXCR2	ENST00000318507.7 link	c.786C>T	p.Leu262Leu	synonymous_variant	Exon 3 of 3	1	NM_001557.4	ENSP00000319635.2	P25025
ENSG00000305582	ENST00000811769.1 link	n.152+4303G>A		intron_variant	Intron 2 of 2
ENSG00000305582	ENST00000811770.1 link	n.208+4303G>A		intron_variant	Intron 3 of 3
CXCR2	ENST00000453237.5 link	c.*184C>T		downstream_gene_variant		1		ENSP00000413686.1	C9JW47

Frequencies

GnomAD3 genomes

AF:

0.533

AC:

80960

AN:

151824

Hom.:

22350

Cov.:

show subpopulations

Gnomad AFR

AF:

0.666

Gnomad AMI

AF:

0.688

Gnomad AMR

AF:

0.524

Gnomad ASJ

AF:

0.574

Gnomad EAS

AF:

0.326

Gnomad SAS

AF:

0.498

Gnomad FIN

AF:

0.398

Gnomad MID

AF:

0.684

Gnomad NFE

AF:

0.488

Gnomad OTH

AF:

0.564

GnomAD2 exomes

AF:

0.483

AC:

121474

AN:

251420

AF XY:

0.485

show subpopulations

Gnomad AFR exome

AF:

0.666

Gnomad AMR exome

AF:

0.470

Gnomad ASJ exome

AF:

0.561

Gnomad EAS exome

AF:

0.326

Gnomad FIN exome

AF:

0.406

Gnomad NFE exome

AF:

0.491

Gnomad OTH exome

AF:

0.518

GnomAD4 exome

AF:

0.484

AC:

707995

AN:

1461846

Hom.:

173672

Cov.:

AF XY:

0.485

AC XY:

352516

AN XY:

727224

show subpopulations

African (AFR)

AF:

0.675

AC:

22592

AN:

33480

American (AMR)

AF:

0.480

AC:

21452

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.566

AC:

14788

AN:

26136

East Asian (EAS)

AF:

0.317

AC:

12565

AN:

39680

South Asian (SAS)

AF:

0.485

AC:

41832

AN:

86258

European-Finnish (FIN)

AF:

0.403

AC:

21542

AN:

53394

Middle Eastern (MID)

AF:

0.654

AC:

3775

AN:

5768

European-Non Finnish (NFE)

AF:

0.485

AC:

538857

AN:

1112010

Other (OTH)

AF:

0.507

AC:

30592

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

27055

54110

81166

108221

135276

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15836

31672

47508

63344

79180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.533

AC:

81019

AN:

151942

Hom.:

22382

Cov.:

AF XY:

0.528

AC XY:

39206

AN XY:

74240

show subpopulations

African (AFR)

AF:

0.665

AC:

27558

AN:

41430

American (AMR)

AF:

0.523

AC:

7987

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.574

AC:

1989

AN:

3468

East Asian (EAS)

AF:

0.326

AC:

1675

AN:

5134

South Asian (SAS)

AF:

0.499

AC:

2398

AN:

4808

European-Finnish (FIN)

AF:

0.398

AC:

4211

AN:

10574

Middle Eastern (MID)

AF:

0.694

AC:

204

AN:

294

European-Non Finnish (NFE)

AF:

0.488

AC:

33184

AN:

67948

Other (OTH)

AF:

0.564

AC:

1186

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1849

3698

5548

7397

9246

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

694

1388

2082

2776

3470

<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:

0.520

Hom.:

9002

Bravo

AF:

0.546

EpiCase

AF:

0.494

EpiControl

AF:

0.511

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 75% of patients studied by a panel of primary immunodeficiencies. Number of patients: 71. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

2.1

(source)

DANN

Benign

0.64

PhyloP100

0.95

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over