NM_000211.5:c.24G>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000211.5(ITGB2):c.24G>T(p.Leu8Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 1,613,330 control chromosomes in the GnomAD database, including 40,682 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3643 hom., cov: 33)

Exomes 𝑓: 0.22 ( 37039 hom. )

Consequence

ITGB2
NM_000211.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5O:2

Conservation

PhyloP100: -0.915

Publications

10 publications found

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 Gene-Disease associations (from GenCC):

leukocyte adhesion deficiency 1
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

ITGB2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 21-44910759-C-A is Benign according to our data. Variant chr21-44910759-C-A is described in ClinVar as Benign. ClinVar VariationId is 100753.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.915 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB2	NM_000211.5 link	c.24G>T	p.Leu8Leu	synonymous_variant	Exon 2 of 16	ENST00000652462.1	NP_000202.3	P05107A0A494C0X7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB2	ENST00000652462.1 link	c.24G>T	p.Leu8Leu	synonymous_variant	Exon 2 of 16		NM_000211.5	ENSP00000498780.1		A0A494C0X7

Frequencies

GnomAD3 genomes

AF:

0.212

AC:

32261

AN:

152110

Hom.:

3638

Cov.:

show subpopulations

Gnomad AFR

AF:

0.224

Gnomad AMI

AF:

0.232

Gnomad AMR

AF:

0.154

Gnomad ASJ

AF:

0.321

Gnomad EAS

AF:

0.0575

Gnomad SAS

AF:

0.356

Gnomad FIN

AF:

0.194

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.216

Gnomad OTH

AF:

0.230

GnomAD2 exomes

AF:

0.211

AC:

52502

AN:

249404

AF XY:

0.223

show subpopulations

Gnomad AFR exome

AF:

0.225

Gnomad AMR exome

AF:

0.106

Gnomad ASJ exome

AF:

0.297

Gnomad EAS exome

AF:

0.0477

Gnomad FIN exome

AF:

0.190

Gnomad NFE exome

AF:

0.220

Gnomad OTH exome

AF:

0.228

GnomAD4 exome

AF:

0.217

AC:

317345

AN:

1461102

Hom.:

37039

Cov.:

AF XY:

0.223

AC XY:

161738

AN XY:

726846

show subpopulations

African (AFR)

AF:

0.226

AC:

7555

AN:

33476

American (AMR)

AF:

0.112

AC:

5006

AN:

44658

Ashkenazi Jewish (ASJ)

AF:

0.302

AC:

7881

AN:

26098

East Asian (EAS)

AF:

0.0524

AC:

2080

AN:

39662

South Asian (SAS)

AF:

0.362

AC:

31161

AN:

86188

European-Finnish (FIN)

AF:

0.189

AC:

10057

AN:

53304

Middle Eastern (MID)

AF:

0.273

AC:

1576

AN:

5766

European-Non Finnish (NFE)

AF:

0.215

AC:

238957

AN:

1111584

Other (OTH)

AF:

0.217

AC:

13072

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

13857

27715

41572

55430

69287

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8218

16436

24654

32872

41090

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.212

AC:

32289

AN:

152228

Hom.:

3643

Cov.:

AF XY:

0.213

AC XY:

15866

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.224

AC:

9321

AN:

41528

American (AMR)

AF:

0.153

AC:

2348

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.321

AC:

1113

AN:

3470

East Asian (EAS)

AF:

0.0571

AC:

296

AN:

5186

South Asian (SAS)

AF:

0.356

AC:

1720

AN:

4828

European-Finnish (FIN)

AF:

0.194

AC:

2061

AN:

10614

Middle Eastern (MID)

AF:

0.228

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.216

AC:

14660

AN:

67988

Other (OTH)

AF:

0.233

AC:

492

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1375

2751

4126

5502

6877

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

354

708

1062

1416

1770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.218

Hom.:

6219

Bravo

AF:

0.204

Asia WGS

AF:

0.192

AC:

670

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5Other:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2Other:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

GenomeConnect, ClinGen

Significance:not provided

Review Status:no classification provided

Collection Method:phenotyping only

Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

Leukocyte adhesion deficiency 1

Benign:2Other:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genomic Research Center, Shahid Beheshti University of Medical Sciences

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 34% of patients studied by a panel of primary immunodeficiencies. Number of patients: 32. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

2.6

(source)

DANN

Benign

0.49

PhyloP100

-0.92

PromoterAI

-0.013

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over