21-44893456-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS1

The NM_000211.5(ITGB2):c.1172C>T(p.Thr391Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000626 in 1,614,170 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. T391T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00047 ( 0 hom. )

Consequence

ITGB2
NM_000211.5 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.813

Publications

5 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, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Orphanet

ITGB2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004409939).

BP6

Variant 21-44893456-G-A is Benign according to our data. Variant chr21-44893456-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 530690.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00216 (329/152338) while in subpopulation AFR AF = 0.00661 (275/41578). AF 95% confidence interval is 0.00597. There are 0 homozygotes in GnomAd4. There are 163 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000211.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ITGB2	NM_000211.5	MANE Select	c.1172C>T	p.Thr391Met	missense	Exon 10 of 16	NP_000202.3	P05107
ITGB2	NM_001127491.3		c.1172C>T	p.Thr391Met	missense	Exon 10 of 16	NP_001120963.2	P05107
ITGB2	NM_001303238.2		c.965C>T	p.Thr322Met	missense	Exon 10 of 16	NP_001290167.1	B4E0R1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ITGB2	ENST00000652462.1	MANE Select	c.1172C>T	p.Thr391Met	missense	Exon 10 of 16	ENSP00000498780.1	A0A494C0X7
ITGB2	ENST00000302347.10	TSL:1	c.1244C>T	p.Thr415Met	missense	Exon 11 of 17	ENSP00000303242.6	A0AAA9WZN5
ITGB2	ENST00000397852.5	TSL:1	c.1172C>T	p.Thr391Met	missense	Exon 9 of 15	ENSP00000380950.1	P05107

Frequencies

GnomAD3 genomes

AF:

0.00214

AC:

326

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00656

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.000764

AC:

192

AN:

251454

AF XY:

0.000618

show subpopulations

Gnomad AFR exome

AF:

0.00523

Gnomad AMR exome

AF:

0.00101

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000761

Gnomad FIN exome

AF:

0.000277

Gnomad NFE exome

AF:

0.000387

Gnomad OTH exome

AF:

0.000814

GnomAD4 exome

AF:

0.000467

AC:

682

AN:

1461832

Hom.:

Cov.:

AF XY:

0.000400

AC XY:

291

AN XY:

727224

show subpopulations

African (AFR)

AF:

0.00526

AC:

176

AN:

33478

American (AMR)

AF:

0.00110

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00139

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000812

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.000187

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000290

AC:

323

AN:

1111980

Other (OTH)

AF:

0.000993

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

121

161

201

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.00216

AC:

329

AN:

152338

Hom.:

Cov.:

AF XY:

0.00219

AC XY:

163

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.00661

AC:

275

AN:

41578

American (AMR)

AF:

0.00137

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00116

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000294

AC:

AN:

68028

Other (OTH)

AF:

0.00284

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

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:

0.00108

Hom.:

Bravo

AF:

0.00235

ESP6500AA

AF:

0.00681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000873

AC:

106

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.000415

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Leukocyte adhesion deficiency 1 (2)

ITGB2-related disorder (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.50

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.78

M_CAP

Benign

0.039

MetaRNN

Benign

0.0044

MetaSVM

Benign

-0.91

PhyloP100

0.81

PrimateAI

Benign

0.31

PROVEAN

Benign

-2.0

REVEL

Benign

0.11

Sift

Benign

0.032

Sift4G

Uncertain

0.054

Vest4

0.14

MVP

0.74

MPC

0.62

ClinPred

0.0084

GERP RS

1.8

gMVP

0.42

Mutation Taster

=83/17

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over