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_000212.3:c.1402G>T

CA400029121

Gene: ITGB3 (HGNC:3690)

Condition: Glanzmann thrombasthenia (MONDO:0100326)

Inheritance Mode: Autosomal recessive inheritance

UUID: 95edf71c-af25-4f7c-9c91-da0934a75e1e

Approved on: 2021-07-14

Published on: 2021-12-23

HGVS expressions

NM_000212.3:c.1402G>T

NC_000017.11:g.47292280G>T

CM000679.2:g.47292280G>T

NC_000017.10:g.45369646G>T

CM000679.1:g.45369646G>T

NC_000017.9:g.42724645G>T

NG_008332.2:g.43439G>T

ENST00000559488.7:c.1402G>T

ENST00000559488.5:c.1402G>T

ENST00000560629.1:n.1367G>T

NM_000212.2:c.1402G>T

Pathogenic

PVS1 PM3_Supporting 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

The ITGB3 nonsense variant NM_000212.3:c.1402G>T (p.Glu468Ter) introduces a premature termination codon in exon 10 of 15 total exons and the resulting mRNA product is predicted to undergo nonsense mediated decay, leading to loss of normal protein function. This variant has been observed in homozygosity in one individual with a phenotype specific for Glanzmann's thrombasthenia (GT) (GT34, PMID: 16463284). Furthermore, this variant is absent from population databases. In summary, this variant meets criteria to be classified as pathogenic for GT. GT-specific criteria applied: PVS1, PM2_Supporting, PM3_Supporting, PP4_Moderate.

PVS1

This variant introduces a termination codon at amino acid position 468 in exon 10 of 15 total exons. The resulting mRNA product is predicted to undergo nonsense mediated decay, leading to loss of normal protein function.

PM3_Supporting

This variant was reported in homozygosity in one individual (GT34 in PMID: 16463284), sufficient to apply PM3_Supporting.

PP4_Moderate

All requirements for PP4_Moderate are met (GT34 in PMID: 16463284): history of bleeding and impaired aggregation to at least two agonists, but normal or only mildly reduced agglutination with ristocetin.

PM2_Supporting

This variant is absent from all population cohorts in gnomAD, ExAC, 1000 Genomes, and ESP.

Curation History

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