2-218136239-C-T

Variant names:

• chr2-218136239-C-T
• rs17844765
• NM_001557.4:c.*355C>T

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.*355C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0143 in 199,492 control chromosomes in the GnomAD database, including 29 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 0.016 (25 hom., cov: 30)
  • Exomes 𝑓: 0.0096 (4 hom.)
• Consequence: CXCR2 NM_001557.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.789
• 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=-0.98).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0159 (2351/147718) while in subpopulation SAS AF = 0.0461 (214/4638). AF 95% confidence interval is 0.0411. There are 25 homozygotes in GnomAd4. There are 1177 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 25 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.*355C>T		3_prime_UTR	Exon 3 of 3	NP_001548.1	P25025
	CXCR2	NM_001168298.2		c.*355C>T		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.*355C>T		3_prime_UTR	Exon 3 of 3	ENSP00000319635.2	P25025
	CXCR2	ENST00000875238.1		c.*355C>T		3_prime_UTR	Exon 3 of 3	ENSP00000545297.1
	CXCR2	ENST00000875239.1		c.*355C>T		3_prime_UTR	Exon 3 of 3	ENSP00000545298.1

Frequencies

GnomAD3 genomes AF: 0.0159 AC: 2345 AN: 147620 Hom.: 24 Cov.: 30

Gnomad AFR AF: 0.0290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00866

Gnomad ASJ AF: 0.00901

Gnomad EAS AF: 0.00235

Gnomad SAS AF: 0.0460

Gnomad FIN AF: 0.00735

Gnomad MID AF: 0.0160

Gnomad NFE AF: 0.0106

Gnomad OTH AF: 0.0104

GnomAD4 exome AF: 0.00956 AC: 495 AN: 51774 Hom.: 4 Cov.: 0 AF XY: 0.0108 AC XY: 279 AN XY: 25718

African (AFR) AF: 0.0184 AC: 24 AN: 1306

American (AMR) AF: 0.0101 AC: 22 AN: 2180

Ashkenazi Jewish (ASJ) AF: 0.0108 AC: 15 AN: 1392

East Asian (EAS) AF: 0.00193 AC: 5 AN: 2584

South Asian (SAS) AF: 0.0446 AC: 54 AN: 1210

European-Finnish (FIN) AF: 0.00895 AC: 143 AN: 15970

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 158

European-Non Finnish (NFE) AF: 0.00864 AC: 212 AN: 24540

Other (OTH) AF: 0.00822 AC: 20 AN: 2434

GnomAD4 genome AF: 0.0159 AC: 2351 AN: 147718 Hom.: 25 Cov.: 30 AF XY: 0.0164 AC XY: 1177 AN XY: 71790

African (AFR) AF: 0.0292 AC: 1158 AN: 39702

American (AMR) AF: 0.00865 AC: 126 AN: 14572

Ashkenazi Jewish (ASJ) AF: 0.00901 AC: 31 AN: 3442

East Asian (EAS) AF: 0.00216 AC: 11 AN: 5094

South Asian (SAS) AF: 0.0461 AC: 214 AN: 4638

European-Finnish (FIN) AF: 0.00735 AC: 72 AN: 9792

Middle Eastern (MID) AF: 0.0139 AC: 4 AN: 288

European-Non Finnish (NFE) AF: 0.0106 AC: 714 AN: 67246

Other (OTH) AF: 0.0103 AC: 21 AN: 2040

Alfa AF: 0.0118 Hom.: 19

Bravo AF: 0.0150

Asia WGS AF: 0.0270 AC: 95 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.4
DANN	Benign	0.34
PhyloP100		-0.79
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: rs17844765; hg19: chr2-219000962;