chr17-44372422-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate
The NM_000419.5(ITGA2B):c.3062T>C(p.Val1021Ala) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 18/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V1021F) has been classified as Uncertain significance.
Frequency
Consequence
NM_000419.5 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ITGA2B | NM_000419.5 | c.3062T>C | p.Val1021Ala | missense_variant, splice_region_variant | 30/30 | ENST00000262407.6 | |
ITGA2B | XM_011524749.2 | c.3113T>C | p.Val1038Ala | missense_variant, splice_region_variant | 29/29 | ||
ITGA2B | XM_011524750.2 | c.3098T>C | p.Val1033Ala | missense_variant, splice_region_variant | 29/29 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ITGA2B | ENST00000262407.6 | c.3062T>C | p.Val1021Ala | missense_variant, splice_region_variant | 30/30 | 1 | NM_000419.5 | P1 | |
ITGA2B | ENST00000648408.1 | c.2378T>C | p.Val793Ala | missense_variant, splice_region_variant | 25/25 | ||||
ITGA2B | ENST00000587295.5 | c.257T>C | p.Val86Ala | missense_variant, splice_region_variant | 3/3 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Glanzmann thrombasthenia Uncertain:1
Uncertain significance, reviewed by expert panel | curation | ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen | Sep 02, 2021 | The NM_000419.5(ITGA2B):c.3062T>C (p.Val1021Ala) missense variant has been reported in at least two Glanzmann thrombasthenia patients (PMID: 21113249). Patient SB displayed mucocutaneous bleeding and impaired aggregation with all agonists except ristocetin, which is highly specific for Glanzmann thrombasthenia. Additionally, αIIbβ3 surface expression was reduced to 23%, as measured by flow cytometry, and there was 12-13% binding to PAC-1. ITGA2B and ITGB3 were sequenced across all exons and intron/exon boundaries (PP4_strong; PMID: 21113249). Patient LN is homozygous for c.3062T>C (PM3_supporting; PMID: 21113249). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). The computational predictor REVEL gives a score of 0.084, which is below the ClinGen PD VCEP threshold of <0.25 and predicts no damaging effect on ITGA2 function (BP4). 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: PP4_strong, PM2_supporting, PM3_supporting, and BP4. (VCEP specifications version 2; date of approval 09/02/2021). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.