chr17-44378349-G-A

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

2

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

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 HGVSp Effect Exon rank MANE Protein UniProt
ITGA2BNM_000419.5 linkc.2094+13C>T intron_variant Intron 20 of 29 ENST00000262407.6 NP_000410.2 P08514-1
ITGA2BXM_011524749.2 linkc.2247+13C>T intron_variant Intron 20 of 28 XP_011523051.2 P08514
ITGA2BXM_011524750.2 linkc.2247+13C>T intron_variant Intron 20 of 28 XP_011523052.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ITGA2BENST00000262407.6 linkc.2094+13C>T intron_variant Intron 20 of 29 1 NM_000419.5 ENSP00000262407.5 P08514-1
ITGA2BENST00000648408.1 linkc.1524+13C>T intron_variant Intron 16 of 24 ENSP00000498119.1 A0A3B3IU79
ITGA2BENST00000592462.5 linkn.889+13C>T intron_variant Intron 9 of 14 5

Frequencies

GnomAD3 genomes
AF:
0.0229
AC:
3484
AN:
152248
Hom.:
94
Cov.:
32
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.:
32
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:
4
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
0
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
0
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.:
93
Cov.:
32
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:
89
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5184
South Asian (SAS)
AF:
0.0116
AC:
56
AN:
4832
European-Finnish (FIN)
AF:
0.0786
AC:
834
AN:
10612
Middle Eastern (MID)
AF:
0.0170
AC:
5
AN:
294
European-Non Finnish (NFE)
AF:
0.0293
AC:
1996
AN:
68034
Other (OTH)
AF:
0.0189
AC:
40
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
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
0
38
76
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.:
35
Bravo
AF:
0.0181
Asia WGS
AF:
0.00549
AC:
19
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
DANN
Benign
0.27
PhyloP100
-0.60
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs12938868; hg19: chr17-42455717; API