17-44372421-G-A

Variant names:

Variant summary

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

The NM_000419.5(ITGA2B):c.3063C>T(p.Val1021Val) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 1,611,870 control chromosomes in the GnomAD database, including 115,978 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 11415 hom., cov: 30)

Exomes 𝑓: 0.38 ( 104563 hom. )

Consequence

ITGA2B
NM_000419.5 splice_region, synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -3.87

Publications

37 publications found

Variant links:

Genes affected

ITGA2B (HGNC:6138): (integrin subunit alpha 2b) This gene encodes a member of the integrin alpha chain family of proteins. The encoded preproprotein is proteolytically processed to generate light and heavy chains that associate through disulfide linkages to form a subunit of the alpha-IIb/beta-3 integrin cell adhesion receptor. This receptor plays a crucial role in the blood coagulation system, by mediating platelet aggregation. Mutations in this gene are associated with platelet-type bleeding disorders, which are characterized by a failure of platelet aggregation, including Glanzmann thrombasthenia. [provided by RefSeq, Jan 2016]

ITGA2B Gene-Disease associations (from GenCC):

platelet-type bleeding disorder 16
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
Glanzmann thrombasthenia
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Glanzmann's thrombasthenia
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics
Glanzmann thrombasthenia 1
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
autosomal dominant macrothrombocytopenia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ITGA2B 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=-0.9).

BP6

Variant 17-44372421-G-A is Benign according to our data. Variant chr17-44372421-G-A is described in ClinVar as Benign. ClinVar VariationId is 256040.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.87 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA2B	NM_000419.5 link	c.3063C>T	p.Val1021Val	splice_region_variant, synonymous_variant	Exon 30 of 30	ENST00000262407.6	NP_000410.2	P08514-1
ITGA2B	XM_011524749.2 link	c.3114C>T	p.Val1038Val	splice_region_variant, synonymous_variant	Exon 29 of 29		XP_011523051.2	P08514
ITGA2B	XM_011524750.2 link	c.3099C>T	p.Val1033Val	splice_region_variant, synonymous_variant	Exon 29 of 29		XP_011523052.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ITGA2B	ENST00000262407.6 link	c.3063C>T	p.Val1021Val	splice_region_variant, synonymous_variant	Exon 30 of 30	1	NM_000419.5	ENSP00000262407.5	P08514-1
ITGA2B	ENST00000648408.1 link	c.2376C>T	p.Val792Val	splice_region_variant, synonymous_variant	Exon 25 of 25			ENSP00000498119.1	A0A3B3IU79
ITGA2B	ENST00000587295.5 link	c.255C>T	p.Val85Val	splice_region_variant, synonymous_variant	Exon 3 of 3	3		ENSP00000467269.1	K7EP83

Frequencies

GnomAD3 genomes

AF:

0.387

AC:

58721

AN:

151574

Hom.:

11419

Cov.:

show subpopulations

Gnomad AFR

AF:

0.389

Gnomad AMI

AF:

0.413

Gnomad AMR

AF:

0.349

Gnomad ASJ

AF:

0.437

Gnomad EAS

AF:

0.439

Gnomad SAS

AF:

0.355

Gnomad FIN

AF:

0.435

Gnomad MID

AF:

0.320

Gnomad NFE

AF:

0.384

Gnomad OTH

AF:

0.363

GnomAD2 exomes

AF:

0.388

AC:

97222

AN:

250774

AF XY:

0.383

show subpopulations

Gnomad AFR exome

AF:

0.394

Gnomad AMR exome

AF:

0.379

Gnomad ASJ exome

AF:

0.425

Gnomad EAS exome

AF:

0.430

Gnomad FIN exome

AF:

0.439

Gnomad NFE exome

AF:

0.383

Gnomad OTH exome

AF:

0.369

GnomAD4 exome

AF:

0.378

AC:

551269

AN:

1460176

Hom.:

104563

Cov.:

AF XY:

0.376

AC XY:

272986

AN XY:

726520

show subpopulations

African (AFR)

AF:

0.370

AC:

12387

AN:

33446

American (AMR)

AF:

0.374

AC:

16696

AN:

44674

Ashkenazi Jewish (ASJ)

AF:

0.426

AC:

11128

AN:

26124

East Asian (EAS)

AF:

0.417

AC:

16547

AN:

39688

South Asian (SAS)

AF:

0.346

AC:

29800

AN:

86202

European-Finnish (FIN)

AF:

0.432

AC:

23067

AN:

53380

Middle Eastern (MID)

AF:

0.351

AC:

2023

AN:

5766

European-Non Finnish (NFE)

AF:

0.375

AC:

416607

AN:

1110552

Other (OTH)

AF:

0.381

AC:

23014

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

15824

31649

47473

63298

79122

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13138

26276

39414

52552

65690

<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:

0.387

AC:

58734

AN:

151694

Hom.:

11415

Cov.:

AF XY:

0.387

AC XY:

28671

AN XY:

74144

show subpopulations

African (AFR)

AF:

0.389

AC:

16061

AN:

41310

American (AMR)

AF:

0.349

AC:

5318

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.437

AC:

1516

AN:

3472

East Asian (EAS)

AF:

0.439

AC:

2249

AN:

5126

South Asian (SAS)

AF:

0.353

AC:

1701

AN:

4814

European-Finnish (FIN)

AF:

0.435

AC:

4587

AN:

10536

Middle Eastern (MID)

AF:

0.320

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.384

AC:

26077

AN:

67886

Other (OTH)

AF:

0.360

AC:

756

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1814

3629

5443

7258

9072

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

568

1136

1704

2272

2840

<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:

0.379

Hom.:

22587

Bravo

AF:

0.380

Asia WGS

AF:

0.402

AC:

1406

AN:

3478

EpiCase

AF:

0.380

EpiControl

AF:

0.367

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Glanzmann thrombasthenia

Benign:2

Feb 03, 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: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 provided

Benign:2

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Glanzmann thrombasthenia 1

Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.0070

(source)

DANN

Benign

0.84

PhyloP100

-3.9

Mutation Taster

=98/2

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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over