2-218134532-G-A

Variant names:

• chr2-218134532-G-A
• rs17844697
• NM_001557.4:c.-25-245G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001557.4(CXCR2):​c.-25-245G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 152,014 control chromosomes in the GnomAD database, including 13,628 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.42 (13628 hom., cov: 32)
• Consequence: CXCR2 NM_001557.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.34
• Publications: 5 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 2-218134532-G-A is Benign according to our data. Variant chr2-218134532-G-A is described in ClinVar as Benign. ClinVar VariationId is 1181067.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCR2	NM_001557.4	c.-25-245G>A		intron_variant	Intron 2 of 2	ENST00000318507.7	NP_001548.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCR2	ENST00000318507.7	c.-25-245G>A		intron_variant	Intron 2 of 2	1	NM_001557.4	ENSP00000319635.2

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63539 AN: 151896 Hom.: 13615 Cov.: 32

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.527

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.618

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.461

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.418 AC: 63570 AN: 152014 Hom.: 13628 Cov.: 32 AF XY: 0.412 AC XY: 30582 AN XY: 74312

African (AFR) AF: 0.416 AC: 17229 AN: 41446

American (AMR) AF: 0.392 AC: 5996 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.527 AC: 1827 AN: 3470

East Asian (EAS) AF: 0.243 AC: 1257 AN: 5178

South Asian (SAS) AF: 0.388 AC: 1867 AN: 4810

European-Finnish (FIN) AF: 0.348 AC: 3673 AN: 10564

Middle Eastern (MID) AF: 0.623 AC: 182 AN: 292

European-Non Finnish (NFE) AF: 0.441 AC: 29952 AN: 67940

Other (OTH) AF: 0.462 AC: 975 AN: 2110

Alfa AF: 0.330 Hom.: 1093

Bravo AF: 0.421

Asia WGS AF: 0.303 AC: 1055 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 18, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.12
DANN	Benign	0.62
PhyloP100		-1.3
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: rs17844697; hg19: chr2-218999255;