GeneBe

17-44372390-C-CCA

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM4PM2_SupportingPM3_Supporting

This summary comes from the ClinGen Evidence Repository: The NM_000419.5(ITGA2B):c.3092_3093dup variant results in a frameshift, p.Glu1032TrpfsTer98, and introduction of a stop codon further than the original. This adds 90 amino acids to the ITGA2B protein. The variant is absent from population databases, including gnomADv2.1.1 (PM2_supporting). It is reported in a compound heterozygous individual with the c.3060+2T>C variant (classified Pathogenic by the PD VCEP; PM3_supporting); however, the individual does not meet criteria for PP4 (PMID:9215749). In summary, this variant meets the criteria to be classified as uncertain significance for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: PM2_Supporting, BP4 (PD VCEP specifications version 2.1). LINK:https://erepo.genome.network/evrepo/ui/classification/CA500260678/MONDO:0010119/011

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

ITGA2B
NM_000419.5 frameshift

Scores

Not classified

Clinical Significance

Uncertain significance reviewed by expert panel P:2U:2

Conservation

PhyloP100: -0.405

Publications

0 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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2
For more information check the summary or visit ClinGen Evidence Repository.
PM3
For more information check the summary or visit ClinGen Evidence Repository.
PM4
For more information check the summary or visit ClinGen Evidence Repository.

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.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
ITGA2B
NM_000419.5
MANE Select
c.3092_3093dupTGp.Glu1032TrpfsTer70
frameshift
Exon 30 of 30NP_000410.2P08514-1

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
ITGA2B
ENST00000262407.6
TSL:1 MANE Select
c.3092_3093dupTGp.Glu1032TrpfsTer70
frameshift
Exon 30 of 30ENSP00000262407.5P08514-1
ITGA2B
ENST00000901307.1
c.2978_2979dupTGp.Glu994TrpfsTer71
frameshift
Exon 29 of 29ENSP00000571366.1
ITGA2B
ENST00000949677.1
c.2975_2976dupTGp.Glu993TrpfsTer70
frameshift
Exon 29 of 29ENSP00000619736.1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.0000294
AC:
43
AN:
1461880
Hom.:
0
Cov.:
30
AF XY:
0.0000220
AC XY:
16
AN XY:
727242
show subpopulations
African (AFR)
AF:
0.0000299
AC:
1
AN:
33480
American (AMR)
AF:
0.00
AC:
0
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39698
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86256
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53420
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.0000333
AC:
37
AN:
1112004
Other (OTH)
AF:
0.0000828
AC:
5
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.474
Heterozygous variant carriers
0
2
4
7
9
11
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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
Cov.:
31
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000378
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

ClinVar submissions
Significance:Uncertain significance
Revision:reviewed by expert panel
View on ClinVar
Pathogenic
VUS
Benign
Condition
-
2
-
Glanzmann thrombasthenia (2)
1
-
-
Platelet-type bleeding disorder 16 (1)
1
-
-
Platelet-type bleeding disorder 16;CN300358:Glanzmann thrombasthenia 1 (1)

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
PhyloP100
-0.41
Mutation Taster
=7/193
disease causing

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs2048504826; hg19: chr17-42449758; API