2-218135569-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001557.4(CXCR2):c.768C>T(p.Val256Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.044 in 1,614,106 control chromosomes in the GnomAD database, including 1,867 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.041 ( 138 hom., cov: 32)

Exomes 𝑓: 0.044 ( 1729 hom. )

Consequence

CXCR2
NM_001557.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.763

Publications

12 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: Ambry Genetics, Orphanet

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 2-218135569-C-T is Benign according to our data. Variant chr2-218135569-C-T is described in ClinVar as Benign. ClinVar VariationId is 1168916.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.763 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0867 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001557.4. 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
	CXCR2	NM_001557.4	MANE Select	c.768C>T	p.Val256Val	synonymous	Exon 3 of 3	NP_001548.1	P25025
	CXCR2	NM_001168298.2		c.768C>T	p.Val256Val	synonymous	Exon 4 of 4	NP_001161770.1	P25025

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CXCR2	ENST00000318507.7	TSL:1 MANE Select	c.768C>T	p.Val256Val	synonymous	Exon 3 of 3	ENSP00000319635.2	P25025
CXCR2	ENST00000875238.1		c.768C>T	p.Val256Val	synonymous	Exon 3 of 3	ENSP00000545297.1
CXCR2	ENST00000875239.1		c.768C>T	p.Val256Val	synonymous	Exon 3 of 3	ENSP00000545298.1

Frequencies

GnomAD3 genomes

AF:

0.0409

AC:

6224

AN:

152108

Hom.:

137

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0362

Gnomad AMI

AF:

0.0384

Gnomad AMR

AF:

0.0304

Gnomad ASJ

AF:

0.0789

Gnomad EAS

AF:

0.0319

Gnomad SAS

AF:

0.0940

Gnomad FIN

AF:

0.0332

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0423

Gnomad OTH

AF:

0.0431

GnomAD2 exomes

AF:

0.0467

AC:

11732

AN:

251480

AF XY:

0.0502

show subpopulations

Gnomad AFR exome

AF:

0.0380

Gnomad AMR exome

AF:

0.0268

Gnomad ASJ exome

AF:

0.0728

Gnomad EAS exome

AF:

0.0341

Gnomad FIN exome

AF:

0.0317

Gnomad NFE exome

AF:

0.0432

Gnomad OTH exome

AF:

0.0502

GnomAD4 exome

AF:

0.0443

AC:

64820

AN:

1461880

Hom.:

1729

Cov.:

AF XY:

0.0462

AC XY:

33591

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.0409

AC:

1369

AN:

33478

American (AMR)

AF:

0.0271

AC:

1210

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0712

AC:

1860

AN:

26136

East Asian (EAS)

AF:

0.0221

AC:

877

AN:

39696

South Asian (SAS)

AF:

0.0957

AC:

8253

AN:

86258

European-Finnish (FIN)

AF:

0.0323

AC:

1723

AN:

53418

Middle Eastern (MID)

AF:

0.0621

AC:

358

AN:

5768

European-Non Finnish (NFE)

AF:

0.0416

AC:

46222

AN:

1112006

Other (OTH)

AF:

0.0488

AC:

2948

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

4478

8956

13434

17912

22390

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1780

3560

5340

7120

8900

<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:

0.0409

AC:

6232

AN:

152226

Hom.:

138

Cov.:

AF XY:

0.0422

AC XY:

3140

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.0363

AC:

1508

AN:

41530

American (AMR)

AF:

0.0305

AC:

466

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0789

AC:

274

AN:

3472

East Asian (EAS)

AF:

0.0320

AC:

165

AN:

5156

South Asian (SAS)

AF:

0.0939

AC:

452

AN:

4814

European-Finnish (FIN)

AF:

0.0332

AC:

353

AN:

10626

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0423

AC:

2877

AN:

68014

Other (OTH)

AF:

0.0426

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

309

618

926

1235

1544

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

246

328

410

<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:

0.0413

Hom.:

Bravo

AF:

0.0385

Asia WGS

AF:

0.0820

AC:

285

AN:

3478

EpiCase

AF:

0.0493

EpiControl

AF:

0.0493

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.034

(source)

DANN

Benign

0.72

PhyloP100

-0.76

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over