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:c.1612G>T

CA399802424

Gene: ITGA2B (HGNC:3674)

Condition: Glanzmann's thrombasthenia (MONDO:0010119)

Inheritance Mode: Autosomal recessive inheritance

UUID: 9a3e6efe-261b-412b-ab23-fd1ad5dcde27

Approved on: 2020-09-06

Published on: 2021-01-28

HGVS expressions

NM_000419.4:c.1612G>T

NM_000419.3:c.1612G>T

NM_000419.5:c.1612G>T

ENST00000262407.5:c.1612G>T

ENST00000592226.5:n.1085G>T

ENST00000592462.5:n.407G>T

NC_000017.11:g.44380142C>A

CM000679.2:g.44380142C>A

NC_000017.10:g.42457510C>A

CM000679.1:g.42457510C>A

NC_000017.9:g.39813036C>A

NG_008331.1:g.14364G>T

Pathogenic

PM2_Supporting PP4_Moderate PVS1

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 nonsense variant, c.1612G>T (p.Glu538Ter), has been reported in one compound heterozygous proband (PMID: 25539746), with a phenotype highly specific to GT, and is absent from population databases. This nonsense variant occurs in exon 17 and is predicted to result in NMD. In summary, this variant meets criteria to be classified as Pathogenic for GT. GT-specific criteria applied: PVS1, PM2_supporting, PP4_moderate.

PM2_Supporting

This variant is absent from population databases including gnomAD, ExAC, and 1000 Genomes.

PP4_Moderate

One proband has been described in the literature (PMID: 25539746) with a normal platelet count and a history of bleeding. Platelet aggregation was impaired for all agonists except ristocetin. Based on flow cytometry, αIIbβ3 expression was between 5% and 20% and exhibited no binding of PAC-1 activation-specific anti- αIIbβ3 antibody.

PVS1

This nonsense variant occurs in exon 17 of 30 and is predicted to result in NMD.

Curation History

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