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 (★★).

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: 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 -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 id 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 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ITGA2B	NM_000419.5 link	c.2094+13C>T	intron_variant	Intron 20 of 29	ENST00000262407.6	NP_000410.2	P08514-1
ITGA2B	XM_011524749.2 link	c.2247+13C>T	intron_variant	Intron 20 of 28		XP_011523051.2	P08514
ITGA2B	XM_011524750.2 link	c.2247+13C>T	intron_variant	Intron 20 of 28		XP_011523052.2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ITGA2B	ENST00000262407.6 link	c.2094+13C>T	intron_variant	Intron 20 of 29	1	NM_000419.5	ENSP00000262407.5	P08514-1
ITGA2B	ENST00000648408.1 link	c.1524+13C>T	intron_variant	Intron 16 of 24			ENSP00000498119.1	A0A3B3IU79
ITGA2B	ENST00000592462.5 link	n.889+13C>T	intron_variant	Intron 9 of 14	5

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

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Glanzmann thrombasthenia

Benign:2

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. -

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over