rs12938868

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000419.5(ITGA2B):c.2094+13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0279 in 1,607,138 control chromosomes in the GnomAD database, including 819 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). The gene ITGA2B is included in the ClinGen Criteria Specification Registry.

Frequency

Genomes: 𝑓 0.023 ( 93 hom., cov: 32)

Exomes 𝑓: 0.028 ( 726 hom. )

Consequence

ITGA2B
NM_000419.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.599

Publications

3 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
Glanzmann thrombasthenia
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Glanzmann's thrombasthenia
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet
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

Specifications for ITGA2B are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 17-44378349-G-A is Benign according to our data. Variant chr17-44378349-G-A is described in ClinVar as Benign. ClinVar VariationId is 256038.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0229 (3483/152366) while in subpopulation NFE AF = 0.0293 (1996/68034). AF 95% confidence interval is 0.0283. There are 93 homozygotes in GnomAd4. There are 1807 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 93 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000419.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA2B	NM_000419.5	MANE Select	c.2094+13C>T		intron	N/A	NP_000410.2	P08514-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ITGA2B	ENST00000262407.6	TSL:1 MANE Select	c.2094+13C>T	intron	N/A	ENSP00000262407.5	P08514-1
ITGA2B	ENST00000901307.1		c.2094+13C>T	intron	N/A	ENSP00000571366.1
ITGA2B	ENST00000949677.1		c.2094+13C>T	intron	N/A	ENSP00000619736.1

Frequencies

GnomAD3 genomes

AF:

0.0229

AC:

3484

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00446

Gnomad AMI

AF:

0.0647

Gnomad AMR

AF:

0.0143

Gnomad ASJ

AF:

0.0256

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0116

Gnomad FIN

AF:

0.0786

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0293

Gnomad OTH

AF:

0.0191

GnomAD2 exomes

AF:

0.0261

AC:

6395

AN:

244964

AF XY:

0.0265

show subpopulations

Gnomad AFR exome

AF:

0.00437

Gnomad AMR exome

AF:

0.0122

Gnomad ASJ exome

AF:

0.0300

Gnomad EAS exome

AF:

0.000110

Gnomad FIN exome

AF:

0.0719

Gnomad NFE exome

AF:

0.0327

Gnomad OTH exome

AF:

0.0303

GnomAD4 exome

AF:

0.0284

AC:

41329

AN:

1454772

Hom.:

726

Cov.:

AF XY:

0.0278

AC XY:

20066

AN XY:

722730

show subpopulations

African (AFR)

AF:

0.00459

AC:

153

AN:

33346

American (AMR)

AF:

0.0133

AC:

590

AN:

44510

Ashkenazi Jewish (ASJ)

AF:

0.0307

AC:

796

AN:

25940

East Asian (EAS)

AF:

0.000101

AC:

AN:

39588

South Asian (SAS)

AF:

0.0104

AC:

894

AN:

85574

European-Finnish (FIN)

AF:

0.0751

AC:

3974

AN:

52896

Middle Eastern (MID)

AF:

0.0420

AC:

183

AN:

4356

European-Non Finnish (NFE)

AF:

0.0299

AC:

33189

AN:

1108602

Other (OTH)

AF:

0.0258

AC:

1546

AN:

59960

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

2215

4431

6646

8862

11077

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1220

2440

3660

4880

6100

<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:

0.0229

AC:

3483

AN:

152366

Hom.:

Cov.:

AF XY:

0.0243

AC XY:

1807

AN XY:

74508

show subpopulations

African (AFR)

AF:

0.00445

AC:

185

AN:

41600

American (AMR)

AF:

0.0143

AC:

219

AN:

15314

Ashkenazi Jewish (ASJ)

AF:

0.0256

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.0116

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0786

AC:

834

AN:

10612

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0293

AC:

1996

AN:

68034

Other (OTH)

AF:

0.0189

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

180

360

541

721

901

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

152

190

<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:

0.0216

Hom.:

Bravo

AF:

0.0181

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Glanzmann thrombasthenia (2)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.45

(source)

DANN

Benign

0.27

PhyloP100

-0.60

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over