Evidence Repository - GenboreeKB

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_000419.5:c.2421G>A

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA399796017

1330347 (ClinVar)

Gene: ITGA2B

Condition: Glanzmann thrombasthenia

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: aa7d79b1-e818-41c1-87d1-167064cb3959

Approved on: 2021-09-03

Published on: 2021-12-23

HGVS expressions

NM_000419.5:c.2421G>A

NC_000017.11:g.44376112C>T

CM000679.2:g.44376112C>T

NC_000017.10:g.42453480C>T

CM000679.1:g.42453480C>T

NC_000017.9:g.39809006C>T

NG_008331.1:g.18394G>A

ENST00000262407.6:c.2421G>A

ENST00000648408.1:n.1852G>A

ENST00000262407.5:c.2421G>A

ENST00000587295.5:n.73G>A

ENST00000592462.5:n.1216G>A

NM_000419.3:c.2421G>A

NM_000419.4:c.2421G>A

NM_000419.5(ITGA2B):c.2421G>A (p.Trp807Ter)

Pathogenic

PM3_Supporting PVS1 PP4_Moderate PM2_Supporting

Evidence Links 0

Expert Panel

Platelet Disorders VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Platelet Disorders VCEP

NM_000419.5(ITGA2B):c.2421G>A (p.Trp807Ter) is a nonsense variant located on exon 24 which is predicted to result in NMD. It is absent from all large population cohorts (gnomAD). This variant has been reported to occur in homozygous state in one proband who meets the diagnostic criteria for the GT phenotype (PMID: 25728920). This variant meets GT specific criteria for PVS1, PP4_moderate, PM2_supporting, and PM3_supporting and is therefore classified as Pathogenic.

PM3_Supporting

This variant was reported to occur in homozygous state in one proband. (PMID:25728920) 0.5 points

PVS1

p.Trp807* is a nonsense variant located on exon 24 of 30 which is predicted to result in NMD.

PP4_Moderate

One individual with the p.Trp807Ter variant in homozygous state presented with significant mucocutaneous bleeding. Platelet aggregometry demonstrated absence of platelet aggregation with 3 platelet agonists and normal aggregation with ristocetin. Information regarding surface expression of αIIbβ3 by flowcytometry was not available. Sanger sequencing ensured coverage of exons and splice sites of the ITGA2B and ITGB3 genes as well as untranslated regions (UTR). PMID:25728920 PP4_moderate applied.

PM2_Supporting

This variant is absent from population databases including gnomAD.

Curation History

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.