17-44372199-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000419.5(ITGA2B):c.*165T>C variant causes a 3 prime UTR change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★★).
Frequency
Genomes: not found (cov: 31)
Consequence
ITGA2B
NM_000419.5 3_prime_UTR
NM_000419.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 4.07
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.45).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ITGA2B | NM_000419.5 | c.*165T>C | 3_prime_UTR_variant | 30/30 | ENST00000262407.6 | ||
ITGA2B | XM_011524749.2 | c.*165T>C | 3_prime_UTR_variant | 29/29 | |||
ITGA2B | XM_011524750.2 | c.*165T>C | 3_prime_UTR_variant | 29/29 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ITGA2B | ENST00000262407.6 | c.*165T>C | 3_prime_UTR_variant | 30/30 | 1 | NM_000419.5 | P1 | ||
ITGA2B | ENST00000587295.5 | c.*165T>C | 3_prime_UTR_variant | 3/3 | 3 | ||||
ITGA2B | ENST00000648408.1 | c.*165T>C | 3_prime_UTR_variant | 25/25 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD4 exome Cov.: 6
GnomAD4 exome
Cov.:
6
GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: reviewed by expert panel
LINK: link
Submissions by phenotype
Glanzmann thrombasthenia Uncertain:1
Uncertain significance, reviewed by expert panel | curation | ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen | Jun 02, 2022 | The NM_000419.5(ITGA2B):c.*165T>C 3'UTR variant was identified homozygous (PM3_supporting) in at least one patient (GT75 in PMID: 25728920) who displayed mucocutaneous bleeding and impaired aggregation with all agonists except ristocetin, which is highly specific for Glanzmann thrombasthenia. Additionally, alphaIIbbeta3 surface expression was reduced to <5%, as measured by flow cytometry (PP4_strong). This variant is absent from gnomAD v3.1.2 (PM2_Supporting). ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: PP4_strong, PM2_supporting, PM3_supporting. (VCEP specifications version 2.1). These criteria reach Likely Pathogenic however, to our knowledge, there is no known disease mechanism for 3'UTR variants in Glanzmann thrombasthenia. In the absence of additional cases or functional data the ClinGen PD VCEP classifies this variant as uncertain significance for autosomal recessive Glanzmann Thrombasthenia. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.