Variant 21-44908184-T-C 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.148-1089A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.847 in 719,108 control chromosomes in the GnomAD database, including 259,384 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.87 ( 58166 hom., cov: 31)

Exomes 𝑓: 0.84 ( 201218 hom. )

Consequence

ITGB2
NM_000211.5 intron

Scores

Splicing: ADA: 0.00002529

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -3.48

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_addAF=-0.906843).

BP6

Variant 21-44908184-T-C is Benign according to our data. Variant chr21-44908184-T-C is described in ClinVar as [Benign]. Clinvar id is 803634.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-44908184-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.959 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.148-1089A>G		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.148-1089A>G		intron_variant			NM_000211.5	ENSP00000498780.1		A0A494C0X7

Frequencies

GnomAD3 genomes

AF:

0.872

AC:

132527

AN:

152022

Hom.:

58100

Cov.:

show subpopulations

Gnomad AFR

AF:

0.967

Gnomad AMI

AF:

0.787

Gnomad AMR

AF:

0.894

Gnomad ASJ

AF:

0.863

Gnomad EAS

AF:

0.773

Gnomad SAS

AF:

0.921

Gnomad FIN

AF:

0.798

Gnomad MID

AF:

0.839

Gnomad NFE

AF:

0.826

Gnomad OTH

AF:

0.863

GnomAD3 exomes

AF:

0.851

AC:

157890

AN:

185526

Hom.:

67506

AF XY:

0.850

AC XY:

87151

AN XY:

102482

show subpopulations

Gnomad AFR exome

AF:

0.970

Gnomad AMR exome

AF:

0.928

Gnomad ASJ exome

AF:

0.859

Gnomad EAS exome

AF:

0.764

Gnomad SAS exome

AF:

0.910

Gnomad FIN exome

AF:

0.786

Gnomad NFE exome

AF:

0.823

Gnomad OTH exome

AF:

0.850

GnomAD4 exome

AF:

0.841

AC:

476683

AN:

566968

Hom.:

201218

Cov.:

AF XY:

0.844

AC XY:

258338

AN XY:

306226

show subpopulations

Gnomad4 AFR exome

AF:

0.967

Gnomad4 AMR exome

AF:

0.923

Gnomad4 ASJ exome

AF:

0.863

Gnomad4 EAS exome

AF:

0.756

Gnomad4 SAS exome

AF:

0.910

Gnomad4 FIN exome

AF:

0.796

Gnomad4 NFE exome

AF:

0.825

Gnomad4 OTH exome

AF:

0.846

GnomAD4 genome

AF:

0.872

AC:

132651

AN:

152140

Hom.:

58166

Cov.:

AF XY:

0.872

AC XY:

64848

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.967

Gnomad4 AMR

AF:

0.895

Gnomad4 ASJ

AF:

0.863

Gnomad4 EAS

AF:

0.773

Gnomad4 SAS

AF:

0.921

Gnomad4 FIN

AF:

0.798

Gnomad4 NFE

AF:

0.826

Gnomad4 OTH

AF:

0.861

Alfa

AF:

0.839

Hom.:

80445

Bravo

AF:

0.879

TwinsUK

AF:

0.819

AC:

3038

ALSPAC

AF:

0.819

AC:

3156

ESP6500AA

AF:

0.975

AC:

1666

ESP6500EA

AF:

0.831

AC:

3260

ExAC

AF:

0.831

AC:

91552

Asia WGS

AF:

0.879

AC:

3058

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

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 99% of patients studied by a panel of primary immunodeficiencies. Number of patients: 94. Only high quality variants are reported. -

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

Mendelics

May 28, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.91

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.54

DANN

Benign

0.31

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0012

GERP RS

-2.3

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000025

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.010

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