Variant 21-44886223-G-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.*145C>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 0.174 in 802,898 control chromosomes in the GnomAD database, including 13,567 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1840 hom., cov: 32)

Exomes 𝑓: 0.18 ( 11727 hom. )

Consequence

ITGB2
NM_000211.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.227

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:

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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_noAF=-0.87).

BP6

Variant 21-44886223-G-T is Benign according to our data. Variant chr21-44886223-G-T is described in ClinVar as [Benign]. Clinvar id is 340133.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-44886223-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.267 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.*145C>A		3_prime_UTR_variant	16/16	ENST00000652462.1	NP_000202.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGB2	ENST00000652462.1 linkuse as main transcript	c.*145C>A		3_prime_UTR_variant	16/16		NM_000211.5	ENSP00000498780	P1

Frequencies

GnomAD3 genomes

AF:

0.137

AC:

20787

AN:

151924

Hom.:

1834

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0362

Gnomad AMI

AF:

0.112

Gnomad AMR

AF:

0.0959

Gnomad ASJ

AF:

0.123

Gnomad EAS

AF:

0.227

Gnomad SAS

AF:

0.278

Gnomad FIN

AF:

0.201

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.181

Gnomad OTH

AF:

0.136

GnomAD4 exome

AF:

0.183

AC:

118858

AN:

650856

Hom.:

11727

Cov.:

AF XY:

0.187

AC XY:

64844

AN XY:

346014

show subpopulations

Gnomad4 AFR exome

AF:

0.0344

Gnomad4 AMR exome

AF:

0.0878

Gnomad4 ASJ exome

AF:

0.131

Gnomad4 EAS exome

AF:

0.230

Gnomad4 SAS exome

AF:

0.263

Gnomad4 FIN exome

AF:

0.201

Gnomad4 NFE exome

AF:

0.182

Gnomad4 OTH exome

AF:

0.173

GnomAD4 genome

AF:

0.137

AC:

20801

AN:

152042

Hom.:

1840

Cov.:

AF XY:

0.140

AC XY:

10386

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.0361

Gnomad4 AMR

AF:

0.0958

Gnomad4 ASJ

AF:

0.123

Gnomad4 EAS

AF:

0.227

Gnomad4 SAS

AF:

0.279

Gnomad4 FIN

AF:

0.201

Gnomad4 NFE

AF:

0.181

Gnomad4 OTH

AF:

0.141

Alfa

AF:

0.0923

Hom.:

203

Bravo

AF:

0.124

ClinVar

Significance: Benign

Submissions summary: Benign:4

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	This variant is associated with the following publications: (PMID: 23921155) -

Leukocyte adhesion deficiency 1

Benign:2

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	Labcorp Genetics (formerly Invitae), Labcorp	Jan 02, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.7

DANN

Benign

0.46

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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