chr2-218136243-G-A

Variant names:

• chr2-218136243-G-A
• rs1126580
• NM_001557.4:c.*359G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001557.4(CXCR2):​c.*359G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 191,236 control chromosomes in the GnomAD database, including 16,342 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 0.42 (13386 hom., cov: 27)
  • Exomes 𝑓: 0.36 (2956 hom.)
• Consequence: CXCR2 NM_001557.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23
• Publications: 33 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: Orphanet, Ambry Genetics

ENSG00000305582 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCR2	NM_001557.4	c.*359G>A		3_prime_UTR_variant	Exon 3 of 3	ENST00000318507.7	NP_001548.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCR2	ENST00000318507.7	c.*359G>A		3_prime_UTR_variant	Exon 3 of 3	1	NM_001557.4	ENSP00000319635.2
ENSG00000305582	ENST00000811769.1	n.152+3647C>T		intron_variant	Intron 2 of 2
ENSG00000305582	ENST00000811770.1	n.208+3647C>T		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.417 AC: 62514 AN: 149926 Hom.: 13373 Cov.: 27

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.672

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.526

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.602

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.460

GnomAD4 exome AF: 0.356 AC: 14646 AN: 41198 Hom.: 2956 Cov.: 0 AF XY: 0.357 AC XY: 7266 AN XY: 20372

African (AFR) AF: 0.395 AC: 358 AN: 906

American (AMR) AF: 0.267 AC: 461 AN: 1726

Ashkenazi Jewish (ASJ) AF: 0.479 AC: 441 AN: 920

East Asian (EAS) AF: 0.173 AC: 335 AN: 1932

South Asian (SAS) AF: 0.285 AC: 282 AN: 988

European-Finnish (FIN) AF: 0.346 AC: 5349 AN: 15458

Middle Eastern (MID) AF: 0.565 AC: 52 AN: 92

European-Non Finnish (NFE) AF: 0.386 AC: 6752 AN: 17488

Other (OTH) AF: 0.365 AC: 616 AN: 1688

GnomAD4 genome AF: 0.417 AC: 62543 AN: 150038 Hom.: 13386 Cov.: 27 AF XY: 0.410 AC XY: 29978 AN XY: 73120

African (AFR) AF: 0.413 AC: 16759 AN: 40546

American (AMR) AF: 0.392 AC: 5910 AN: 15076

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 1821 AN: 3462

East Asian (EAS) AF: 0.241 AC: 1236 AN: 5128

South Asian (SAS) AF: 0.388 AC: 1840 AN: 4740

European-Finnish (FIN) AF: 0.340 AC: 3450 AN: 10140

Middle Eastern (MID) AF: 0.610 AC: 178 AN: 292

European-Non Finnish (NFE) AF: 0.440 AC: 29782 AN: 67670

Other (OTH) AF: 0.461 AC: 958 AN: 2078

Alfa AF: 0.435 Hom.: 39235

Bravo AF: 0.422

Asia WGS AF: 0.305 AC: 1060 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.42
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs1126580; hg19: chr2-219000966;