Variant rs2230529 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000211.5(ITGB2):c.1101C>A(p.Val367=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 1,613,646 control chromosomes in the GnomAD database, including 48,887 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4337 hom., cov: 32)

Exomes 𝑓: 0.24 ( 44550 hom. )

Consequence

ITGB2
NM_000211.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6O:1

Conservation

PhyloP100: -0.249

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 21-44893527-G-T is Benign according to our data. Variant chr21-44893527-G-T is described in ClinVar as [Benign]. Clinvar id is 100746.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-44893527-G-T is described in Lovd as [Benign]. Variant chr21-44893527-G-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.249 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGB2	NM_000211.5 linkuse as main transcript	c.1101C>A	p.Val367=	synonymous_variant	10/16	ENST00000652462.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGB2	ENST00000652462.1 linkuse as main transcript	c.1101C>A	p.Val367=	synonymous_variant	10/16		NM_000211.5	P1

Frequencies

GnomAD3 genomes

AF:

0.233

AC:

35464

AN:

152008

Hom.:

4329

Cov.:

show subpopulations

Gnomad AFR

AF:

0.225

Gnomad AMI

AF:

0.270

Gnomad AMR

AF:

0.216

Gnomad ASJ

AF:

0.275

Gnomad EAS

AF:

0.103

Gnomad SAS

AF:

0.250

Gnomad FIN

AF:

0.169

Gnomad MID

AF:

0.351

Gnomad NFE

AF:

0.257

Gnomad OTH

AF:

0.269

GnomAD3 exomes

AF:

0.224

AC:

56404

AN:

251326

Hom.:

7003

AF XY:

0.233

AC XY:

31615

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.225

Gnomad AMR exome

AF:

0.139

Gnomad ASJ exome

AF:

0.288

Gnomad EAS exome

AF:

0.108

Gnomad SAS exome

AF:

0.267

Gnomad FIN exome

AF:

0.170

Gnomad NFE exome

AF:

0.261

Gnomad OTH exome

AF:

0.255

GnomAD4 exome

AF:

0.242

AC:

353317

AN:

1461520

Hom.:

44550

Cov.:

AF XY:

0.244

AC XY:

177186

AN XY:

727080

show subpopulations

Gnomad4 AFR exome

AF:

0.226

Gnomad4 AMR exome

AF:

0.145

Gnomad4 ASJ exome

AF:

0.286

Gnomad4 EAS exome

AF:

0.0967

Gnomad4 SAS exome

AF:

0.263

Gnomad4 FIN exome

AF:

0.173

Gnomad4 NFE exome

AF:

0.251

Gnomad4 OTH exome

AF:

0.241

GnomAD4 genome

AF:

0.233

AC:

35484

AN:

152126

Hom.:

4337

Cov.:

AF XY:

0.230

AC XY:

17134

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.225

Gnomad4 AMR

AF:

0.216

Gnomad4 ASJ

AF:

0.275

Gnomad4 EAS

AF:

0.104

Gnomad4 SAS

AF:

0.250

Gnomad4 FIN

AF:

0.169

Gnomad4 NFE

AF:

0.257

Gnomad4 OTH

AF:

0.266

Alfa

AF:

0.253

Hom.:

4545

Bravo

AF:

0.232

Asia WGS

AF:

0.178

AC:

620

AN:

3478

EpiCase

AF:

0.268

EpiControl

AF:

0.278

ClinVar

Significance: Benign

Submissions summary: Benign:6Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Leukocyte adhesion deficiency 1

Benign:3Other: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. -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
not provided, no classification provided	literature only	Genomic Research Center, Shahid Beheshti University of Medical Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 19, 2021	- -

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 41% of patients studied by a panel of primary immunodeficiencies. Number of patients: 39. Only high quality variants are reported. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

6.5

DANN

Benign

0.80

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