rs13306441

Variant names:

• chr2-218136222-A-G
• rs13306441
• NM_001557.4:c.*338A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001557.4(CXCR2):​c.*338A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0251 in 225,106 control chromosomes in the GnomAD database, including 97 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.025 (56 hom., cov: 30)
  • Exomes 𝑓: 0.026 (41 hom.)
• Consequence: CXCR2 NM_001557.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.377
• Publications: 2 publications found

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

ENSG00000305582 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0246 (3743/152010) while in subpopulation SAS AF = 0.0479 (230/4798). AF 95% confidence interval is 0.0429. There are 56 homozygotes in GnomAd4. There are 1878 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 56 AR gene

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.*338A>G		3_prime_UTR	Exon 3 of 3	NP_001548.1	P25025
	CXCR2	NM_001168298.2		c.*338A>G		3_prime_UTR	Exon 4 of 4	NP_001161770.1	P25025

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCR2	ENST00000318507.7	TSL:1 MANE Select	c.*338A>G		3_prime_UTR	Exon 3 of 3	ENSP00000319635.2	P25025
	CXCR2	ENST00000875238.1		c.*338A>G		3_prime_UTR	Exon 3 of 3	ENSP00000545297.1
	CXCR2	ENST00000875239.1		c.*338A>G		3_prime_UTR	Exon 3 of 3	ENSP00000545298.1

Frequencies

GnomAD3 genomes AF: 0.0246 AC: 3741 AN: 151892 Hom.: 56 Cov.: 30

Gnomad AFR AF: 0.00620

Gnomad AMI AF: 0.0385

Gnomad AMR AF: 0.0219

Gnomad ASJ AF: 0.0700

Gnomad EAS AF: 0.0254

Gnomad SAS AF: 0.0481

Gnomad FIN AF: 0.0260

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0317

Gnomad OTH AF: 0.0332

GnomAD4 exome AF: 0.0262 AC: 1918 AN: 73096 Hom.: 41 Cov.: 0 AF XY: 0.0272 AC XY: 996 AN XY: 36642

African (AFR) AF: 0.00580 AC: 12 AN: 2070

American (AMR) AF: 0.0222 AC: 70 AN: 3150

Ashkenazi Jewish (ASJ) AF: 0.0514 AC: 115 AN: 2236

East Asian (EAS) AF: 0.0118 AC: 52 AN: 4392

South Asian (SAS) AF: 0.0452 AC: 78 AN: 1724

European-Finnish (FIN) AF: 0.0203 AC: 349 AN: 17192

Middle Eastern (MID) AF: 0.0639 AC: 17 AN: 266

European-Non Finnish (NFE) AF: 0.0291 AC: 1112 AN: 38166

Other (OTH) AF: 0.0290 AC: 113 AN: 3900

GnomAD4 genome AF: 0.0246 AC: 3743 AN: 152010 Hom.: 56 Cov.: 30 AF XY: 0.0253 AC XY: 1878 AN XY: 74314

African (AFR) AF: 0.00620 AC: 257 AN: 41444

American (AMR) AF: 0.0219 AC: 334 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.0700 AC: 243 AN: 3470

East Asian (EAS) AF: 0.0257 AC: 133 AN: 5178

South Asian (SAS) AF: 0.0479 AC: 230 AN: 4798

European-Finnish (FIN) AF: 0.0260 AC: 276 AN: 10602

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0317 AC: 2158 AN: 67976

Other (OTH) AF: 0.0329 AC: 69 AN: 2100

Alfa AF: 0.0315 Hom.: 114

Bravo AF: 0.0226

Asia WGS AF: 0.0550 AC: 190 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.6
DANN	Benign	0.40
PhyloP100		0.38
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs13306441; hg19: chr2-219000945;