NM_000211.5:c.162G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_000211.5(ITGB2):c.162G>A(p.Pro54Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00294 in 1,603,324 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0020 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0030 ( 13 hom. )

Consequence

ITGB2
NM_000211.5 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: -4.12

Publications

2 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 21-44907081-C-T is Benign according to our data. Variant chr21-44907081-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 340179. Variant chr21-44907081-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 340179. Variant chr21-44907081-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 340179. Variant chr21-44907081-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 340179. Variant chr21-44907081-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 340179. Variant chr21-44907081-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 340179. Variant chr21-44907081-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 340179. Variant chr21-44907081-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 340179. Variant chr21-44907081-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 340179. Variant chr21-44907081-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 340179. Variant chr21-44907081-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 340179. Variant chr21-44907081-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 340179. Variant chr21-44907081-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 340179. Variant chr21-44907081-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 340179. Variant chr21-44907081-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 340179. Variant chr21-44907081-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 340179. Variant chr21-44907081-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 340179. Variant chr21-44907081-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 340179. Variant chr21-44907081-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 340179. Variant chr21-44907081-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 340179. Variant chr21-44907081-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 340179. Variant chr21-44907081-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 340179. Variant chr21-44907081-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 340179. Variant chr21-44907081-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 340179. Variant chr21-44907081-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 340179. Variant chr21-44907081-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 340179. Variant chr21-44907081-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 340179. Variant chr21-44907081-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 340179.

BP7

Synonymous conserved (PhyloP=-4.12 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.002 (304/152274) while in subpopulation NFE AF = 0.0035 (238/68012). AF 95% confidence interval is 0.00313. There are 1 homozygotes in GnomAd4. There are 125 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB2	NM_000211.5 link	c.162G>A	p.Pro54Pro	synonymous_variant	Exon 4 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.162G>A	p.Pro54Pro	synonymous_variant	Exon 4 of 16		NM_000211.5	ENSP00000498780.1		A0A494C0X7

Frequencies

GnomAD3 genomes

AF:

0.00200

AC:

304

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00350

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.00172

AC:

424

AN:

246452

AF XY:

0.00174

show subpopulations

Gnomad AFR exome

AF:

0.000617

Gnomad AMR exome

AF:

0.000844

Gnomad ASJ exome

AF:

0.00377

Gnomad EAS exome

AF:

0.00120

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00243

Gnomad OTH exome

AF:

0.00133

GnomAD4 exome

AF:

0.00304

AC:

4414

AN:

1451050

Hom.:

Cov.:

AF XY:

0.00292

AC XY:

2102

AN XY:

720052

show subpopulations

African (AFR)

AF:

0.000750

AC:

AN:

33318

American (AMR)

AF:

0.00119

AC:

AN:

44442

Ashkenazi Jewish (ASJ)

AF:

0.00421

AC:

108

AN:

25682

East Asian (EAS)

AF:

0.000557

AC:

AN:

39486

South Asian (SAS)

AF:

0.00191

AC:

163

AN:

85520

European-Finnish (FIN)

AF:

0.0000379

AC:

AN:

52840

Middle Eastern (MID)

AF:

0.000377

AC:

AN:

5306

European-Non Finnish (NFE)

AF:

0.00349

AC:

3856

AN:

1104570

Other (OTH)

AF:

0.00306

AC:

183

AN:

59886

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

211

422

634

845

1056

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

288

432

576

720

<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:

0.00200

AC:

304

AN:

152274

Hom.:

Cov.:

AF XY:

0.00168

AC XY:

125

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.000578

AC:

AN:

41552

American (AMR)

AF:

0.00144

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00231

AC:

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5180

South Asian (SAS)

AF:

0.00124

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00350

AC:

238

AN:

68012

Other (OTH)

AF:

0.00142

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00269

Hom.:

Bravo

AF:

0.00199

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Leukocyte adhesion deficiency 1

Uncertain:1Benign:1

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

not provided

Benign:2

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.18

(source)

DANN

Benign

0.29

PhyloP100

-4.1

Mutation Taster

=100/0

polymorphism

(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