chr2-218125582-GT-G

Position:

• chr2-218125582-GT-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001168298.2(CXCR2):​c.-141+234delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 148,136 control chromosomes in the GnomAD database, including 24,659 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.57 (24657 hom., cov: 0)
  • Exomes 𝑓: 0.42 (2 hom.)
• Consequence: CXCR2 NM_001168298.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.557

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CXCR2	NM_001168298.2	c.-141+234delT		intron_variant			NP_001161770.1
CXCR2	XM_047444190.1	c.-89+234delT		intron_variant			XP_047300146.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CXCR2	ENST00000453237.5	c.-141+224delT		intron_variant		1		ENSP00000413686.1

Frequencies

GnomAD3 genomes AF: 0.569 AC: 84275 AN: 148012 Hom.: 24646 Cov.: 0

Gnomad AFR AF: 0.747

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.545

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.657

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.588

GnomAD4 exome AF: 0.417 AC: 10 AN: 24 Hom.: 2 AF XY: 0.438 AC XY: 7 AN XY: 16

Gnomad4 FIN exome AF: 0.438

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.569 AC: 84324 AN: 148112 Hom.: 24657 Cov.: 0 AF XY: 0.565 AC XY: 40787 AN XY: 72144

Gnomad4 AFR AF: 0.746

Gnomad4 AMR AF: 0.533

Gnomad4 ASJ AF: 0.614

Gnomad4 EAS AF: 0.329

Gnomad4 SAS AF: 0.545

Gnomad4 FIN AF: 0.437

Gnomad4 NFE AF: 0.505

Gnomad4 OTH AF: 0.586

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs35231134; hg19: chr2-218990305;