Variant rs2070947 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001127491.3(ITGB2):c.-4+7726T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 152,340 control chromosomes in the GnomAD database, including 4,491 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 4486 hom., cov: 32)

Exomes 𝑓: 0.22 ( 5 hom. )

Consequence

ITGB2
NM_001127491.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.321

Variant links:

Genes affected

ITGB2 (HGNC:):

ITGB2 links:

ITGB2 (HGNC:6155): (integrin subunit beta 2) This gene encodes an integrin beta chain, which combines with multiple different alpha chains to form different integrin heterodimers. Integrins are integral cell-surface proteins that participate in cell adhesion as well as cell-surface mediated signalling. The encoded protein plays an important role in immune response and defects in this gene cause leukocyte adhesion deficiency. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

ITGB2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 21-44920928-A-G is Benign according to our data. Variant chr21-44920928-A-G is described in ClinVar as [Benign]. Clinvar id is 340189.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-44920928-A-G is described in Lovd as [Benign]. Variant chr21-44920928-A-G is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
ITGB2	NM_001127491.3 linkuse as main transcript	c.-4+7726T>C	intron_variant		NP_001120963.2	P05107A0A494C0X7
ITGB2	NM_000211.5 linkuse as main transcript	c.-111T>C	upstream_gene_variant	ENST00000652462.1	NP_000202.3	P05107A0A494C0X7
ITGB2	NM_001303238.2 linkuse as main transcript	c.-361T>C	upstream_gene_variant		NP_001290167.1	P05107B4E0R1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGB2	ENST00000652462.1 linkuse as main transcript	c.-111T>C		upstream_gene_variant			NM_000211.5	ENSP00000498780.1		A0A494C0X7

Frequencies

GnomAD3 genomes

AF:

0.219

AC:

33283

AN:

152016

Hom.:

4489

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0638

Gnomad AMI

AF:

0.355

Gnomad AMR

AF:

0.261

Gnomad ASJ

AF:

0.240

Gnomad EAS

AF:

0.218

Gnomad SAS

AF:

0.154

Gnomad FIN

AF:

0.218

Gnomad MID

AF:

0.207

Gnomad NFE

AF:

0.305

Gnomad OTH

AF:

0.264

GnomAD4 exome

AF:

0.218

AC:

AN:

206

Hom.:

Cov.:

AF XY:

0.224

AC XY:

AN XY:

170

show subpopulations

Gnomad4 AMR exome

AF:

0.500

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.125

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.233

Gnomad4 OTH exome

AF:

0.167

GnomAD4 genome

AF:

0.219

AC:

33278

AN:

152134

Hom.:

4486

Cov.:

AF XY:

0.212

AC XY:

15788

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.0636

Gnomad4 AMR

AF:

0.260

Gnomad4 ASJ

AF:

0.240

Gnomad4 EAS

AF:

0.217

Gnomad4 SAS

AF:

0.154

Gnomad4 FIN

AF:

0.218

Gnomad4 NFE

AF:

0.305

Gnomad4 OTH

AF:

0.266

Alfa

AF:

0.290

Hom.:

9690

Bravo

AF:

0.218

Asia WGS

AF:

0.183

AC:

637

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Leukocyte adhesion deficiency 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

7.6

DANN

Benign

0.37

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over