2-218125582-GTTT-GTTTT

Position:

• chr2-218125582-GTTT-GTTTT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS1

The NM_001168298.2(CXCR2):​c.-141+234dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00089 (1 hom., cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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 Likely_benign. Variant got -4 ACMG points.

• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000891 (132/148144) while in subpopulation AMR AF= 0.00134 (20/14872). AF 95% confidence interval is 0.000891. There are 1 homozygotes in gnomad4. There are 66 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CXCR2	ENST00000453237.5	c.-141+223_-141+224insT		intron_variant		1		ENSP00000413686.1

Frequencies

GnomAD3 genomes AF: 0.000865 AC: 128 AN: 148044 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.000372

Gnomad AMI AF: 0.00336

Gnomad AMR AF: 0.00135

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000599

Gnomad SAS AF: 0.000642

Gnomad FIN AF: 0.00245

Gnomad MID AF: 0.00654

Gnomad NFE AF: 0.000794

Gnomad OTH AF: 0.00247

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 24 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 16

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.000891 AC: 132 AN: 148144 Hom.: 1 Cov.: 0 AF XY: 0.000915 AC XY: 66 AN XY: 72156

Gnomad4 AFR AF: 0.000470

Gnomad4 AMR AF: 0.00134

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000600

Gnomad4 SAS AF: 0.000643

Gnomad4 FIN AF: 0.00245

Gnomad4 NFE AF: 0.000794

Gnomad4 OTH AF: 0.00245

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;