2-218125576-GTT-GT

Variant summary

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

The ENST00000453237.5(CXCR2):c.-141+222del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 150,788 control chromosomes in the GnomAD database, including 28,044 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.60 (28042 hom., cov: 0)
  • Exomes 𝑓: 0.38 (2 hom.)
• Consequence: CXCR2 ENST00000453237.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.467

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 = 0.776 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CXCR2	NM_001168298.2	c.-141+222del		intron_variant
CXCR2	XM_047444190.1	c.-89+222del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CXCR2	ENST00000453237.5	c.-141+222del		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.597 AC: 89881 AN: 150646 Hom.: 28009 Cov.: 0

Gnomad AFR AF: 0.783

Gnomad AMI AF: 0.723

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.651

Gnomad EAS AF: 0.355

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.621

GnomAD4 exome AF: 0.385 AC: 10 AN: 26 Hom.: 2 AF XY: 0.409 AC XY: 9 AN XY: 22

Gnomad4 AMR exome AF: 0.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.375

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.597 AC: 89952 AN: 150762 Hom.: 28042 Cov.: 0 AF XY: 0.592 AC XY: 43532 AN XY: 73594

Gnomad4 AFR AF: 0.783

Gnomad4 AMR AF: 0.563

Gnomad4 ASJ AF: 0.651

Gnomad4 EAS AF: 0.355

Gnomad4 SAS AF: 0.591

Gnomad4 FIN AF: 0.430

Gnomad4 NFE AF: 0.530

Gnomad4 OTH AF: 0.620

Alfa AF: 0.157 Hom.: 551

Asia WGS AF: 0.479 AC: 1665 AN: 3478

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: rs45493792; hg19: chr2-218990299;