Variant rs5030668 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_000211.5(ITGB2):c.328+15G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,613,630 control chromosomes in the GnomAD database, including 19,359 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1677 hom., cov: 32)

Exomes 𝑓: 0.15 ( 17682 hom. )

Consequence

ITGB2
NM_000211.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -2.84

Variant links:

Genes affected

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:

ITGB2 (HGNC:):

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=-0.88).

BP6

Variant 21-44906900-C-T is Benign according to our data. Variant chr21-44906900-C-T is described in ClinVar as [Benign]. Clinvar id is 340174.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-44906900-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGB2	NM_000211.5 linkuse as main transcript	c.328+15G>A		intron_variant		ENST00000652462.1	NP_000202.3	P05107A0A494C0X7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGB2	ENST00000652462.1 linkuse as main transcript	c.328+15G>A		intron_variant			NM_000211.5	ENSP00000498780.1		A0A494C0X7

Frequencies

GnomAD3 genomes

AF:

0.132

AC:

20040

AN:

152132

Hom.:

1678

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0458

Gnomad AMI

AF:

0.340

Gnomad AMR

AF:

0.219

Gnomad ASJ

AF:

0.168

Gnomad EAS

AF:

0.129

Gnomad SAS

AF:

0.0852

Gnomad FIN

AF:

0.182

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.156

Gnomad OTH

AF:

0.114

GnomAD3 exomes

AF:

0.157

AC:

39354

AN:

250890

Hom.:

3592

AF XY:

0.152

AC XY:

20628

AN XY:

135686

show subpopulations

Gnomad AFR exome

AF:

0.0442

Gnomad AMR exome

AF:

0.269

Gnomad ASJ exome

AF:

0.168

Gnomad EAS exome

AF:

0.132

Gnomad SAS exome

AF:

0.0909

Gnomad FIN exome

AF:

0.176

Gnomad NFE exome

AF:

0.155

Gnomad OTH exome

AF:

0.167

GnomAD4 exome

AF:

0.151

AC:

221135

AN:

1461380

Hom.:

17682

Cov.:

AF XY:

0.150

AC XY:

108699

AN XY:

727016

show subpopulations

Gnomad4 AFR exome

AF:

0.0413

Gnomad4 AMR exome

AF:

0.260

Gnomad4 ASJ exome

AF:

0.169

Gnomad4 EAS exome

AF:

0.110

Gnomad4 SAS exome

AF:

0.0955

Gnomad4 FIN exome

AF:

0.177

Gnomad4 NFE exome

AF:

0.155

Gnomad4 OTH exome

AF:

0.152

GnomAD4 genome

AF:

0.132

AC:

20041

AN:

152250

Hom.:

1677

Cov.:

AF XY:

0.134

AC XY:

9987

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0457

Gnomad4 AMR

AF:

0.219

Gnomad4 ASJ

AF:

0.168

Gnomad4 EAS

AF:

0.129

Gnomad4 SAS

AF:

0.0844

Gnomad4 FIN

AF:

0.182

Gnomad4 NFE

AF:

0.156

Gnomad4 OTH

AF:

0.114

Alfa

AF:

0.138

Hom.:

370

Bravo

AF:

0.131

Asia WGS

AF:

0.120

AC:

419

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jan 24, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 31% of patients studied by a panel of primary immunodeficiencies. Number of patients: 29. Only high quality variants are reported. -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Leukocyte adhesion deficiency 1

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.0060

DANN

Benign

0.36

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

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