Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with ClinVar but not with the Allele Registry data
  • No CSPEC related information was provided by the message!
  • No Criteria Specification was provided in the publication event for the variant classifaction.
  • The Criteria Specification shown below is a best-estimate based on the VCEP, gene, disease, and publication date.

Variant: NM_000419.5(ITGA2B):c.240_241del (p.Glu80fs)

977125 (ClinVar)

Gene: ITGA2B
Condition: Glanzmann thrombasthenia (MONDO:0010119)
Inheritance Mode: Autosomal recessive inheritance
UUID: cf37ba1d-7bdf-406c-91aa-6a6acdd669a6
Approved on: 2022-06-08
Published on: 2022-06-12

HGVS expressions

NM_000419.5(ITGA2B):c.240_241del (p.Glu80fs)
NM_000419.5:c.240_241del

Pathogenic

Met criteria codes 4
PM3_Supporting PVS1 PP4_Strong PM2_Supporting

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Platelet Disorders VCEP
The NM_000419.5(ITGA2B):c.240_241del (p.Glu80fs) frameshift variant occurs in exon 2 of 30 where it creates a premature stop codon and is predicted to result in NMD. At least one patient (P1 in PMID: 34275420) is homozygous for this variant (PM3_supporting) and 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 <5%, as measured by flow cytometry (PP4_strong). It is absent from gnomAD, ExAC, 1000 Genomes, and ESP. In summary, this variant meets criteria to be classified as pathogenic for GT. GT-specific criteria applied: PP4_Strong, PM2_Supporting, PM3_supporting, and PVS1.
Met criteria codes
PM3_Supporting
P1 (PMID: 34275420) is homozygous for this variant. 0.5pt (PM3_supporting)
PVS1
The frameshift variant occurs in exon 2 of 30 where it creates a premature stop codon and is predicted to result in NMD.
PP4_Strong
At least one patient (P1 in PMID: 34275420) with this variant 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 <5%, as measured by flow cytometry. ITGA2B and ITGB3 were sequenced across all exons and intron/exon boundaries. (PP4_strong)
PM2_Supporting
This variant is absent from all population cohorts in gnomAD, ExAC, 1000 Genomes, and ESP.
Curation History
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