Evidence Repository - Clinical Genome Resources

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_000419.4(ITGA2B):c.1750C>T (p.Arg584Ter)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA115834

2892 (ClinVar)

Gene: ITGA2B

Condition: Glanzmann's thrombasthenia

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 1a869768-9193-4b8f-af73-e009889cb07c

Approved on: 2020-09-04

Published on: 2021-01-28

HGVS expressions

NM_000419.4:c.1750C>T

NM_000419.4(ITGA2B):c.1750C>T (p.Arg584Ter)

NC_000017.11:g.44380004G>A

CM000679.2:g.44380004G>A

NC_000017.10:g.42457372G>A

CM000679.1:g.42457372G>A

NC_000017.9:g.39812898G>A

NG_008331.1:g.14502C>T

NM_000419.3:c.1750C>T

NM_000419.5:c.1750C>T

ENST00000262407.5:c.1750C>T

ENST00000592462.5:n.545C>T

Pathogenic

PP4_Strong PVS1

PM3

Evidence Links 0

Expert Panel

Platelet Disorders VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Platelet Disorders VCEP

The NM_000419.4:c.1750C>T that leads to Arg584Ter is a nonsense variant that has been reported in several GT patients meeting phenotype criteria in the homozygous as well as compound heterozygous states (PMIDs: 25728920, 28888044, 22250950, 9215749, 29675921). It is reported at a frequency >0.0001 in the combined gnomAD v3 and v2.1.1 datasets. This nonsense variant occurs in exon 17 out of 30 and is predicted to result in NMD. In summary, this variant meets criteria to be classified as pathogenic. GT-specific codes applied: PVS1, PP4_strong.

PP4_Strong

Arg584Ter is reported in multiple patients in the literature. GT13 from PMID: 25728920 meets phenotype criteria for PP4_strong; including bleeding phenotype, abnormal platelet aggregation with >2 agonists, reduced αIIbβ3 expression on flow cytometry and full sequencing of ITGA2B and ITGB3.

PVS1

This variant is expected to undergo NMD because it is in exon 17 out of 30.

PM3

At least 1 homozygous and several compound heterozygous occurrences are noted in the literature. However, PM3 may not be applied since the variant does not meet PM2.

Curation History

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