Variant chr21-44886246-C-T 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.*122G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 1,002,834 control chromosomes in the GnomAD database, including 22,181 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3090 hom., cov: 31)

Exomes 𝑓: 0.21 ( 19091 hom. )

Consequence

ITGB2
NM_000211.5 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.420

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 21-44886246-C-T is Benign according to our data. Variant chr21-44886246-C-T is described in ClinVar as [Benign]. Clinvar id is 340134.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.227 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.*122G>A		3_prime_UTR_variant	16/16	ENST00000652462.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGB2	ENST00000652462.1 linkuse as main transcript	c.*122G>A		3_prime_UTR_variant	16/16		NM_000211.5	P1

Frequencies

GnomAD3 genomes

AF:

0.196

AC:

29765

AN:

151796

Hom.:

3085

Cov.:

show subpopulations

Gnomad AFR

AF:

0.162

Gnomad AMI

AF:

0.220

Gnomad AMR

AF:

0.189

Gnomad ASJ

AF:

0.234

Gnomad EAS

AF:

0.0840

Gnomad SAS

AF:

0.189

Gnomad FIN

AF:

0.161

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.230

Gnomad OTH

AF:

0.226

GnomAD4 exome

AF:

0.206

AC:

175103

AN:

850920

Hom.:

19091

Cov.:

AF XY:

0.208

AC XY:

92222

AN XY:

444294

show subpopulations

Gnomad4 AFR exome

AF:

0.160

Gnomad4 AMR exome

AF:

0.128

Gnomad4 ASJ exome

AF:

0.248

Gnomad4 EAS exome

AF:

0.0923

Gnomad4 SAS exome

AF:

0.195

Gnomad4 FIN exome

AF:

0.164

Gnomad4 NFE exome

AF:

0.223

Gnomad4 OTH exome

AF:

0.211

GnomAD4 genome

AF:

0.196

AC:

29778

AN:

151914

Hom.:

3090

Cov.:

AF XY:

0.192

AC XY:

14260

AN XY:

74230

show subpopulations

Gnomad4 AFR

AF:

0.162

Gnomad4 AMR

AF:

0.189

Gnomad4 ASJ

AF:

0.234

Gnomad4 EAS

AF:

0.0840

Gnomad4 SAS

AF:

0.189

Gnomad4 FIN

AF:

0.161

Gnomad4 NFE

AF:

0.230

Gnomad4 OTH

AF:

0.223

Alfa

AF:

0.223

Hom.:

2268

Bravo

AF:

0.195

Asia WGS

AF:

0.138

AC:

481

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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:1

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.5

DANN

Benign

0.63

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