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]

Link to SEPIO compliant JSON-LD document

CA400023704

Gene: ITGB3

Condition: Glanzmann's thrombasthenia

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: e113c60d-9ec3-4646-8d50-e6ea99e9f876

Approved on: 2021-06-15

Published on: 2021-08-20

HGVS expressions

NM_000212.3:c.774T>A

NC_000017.11:g.47286419T>A

CM000679.2:g.47286419T>A

NC_000017.10:g.45363785T>A

CM000679.1:g.45363785T>A

NC_000017.9:g.42718784T>A

NG_008332.2:g.37578T>A

ENST00000559488.7:c.774T>A

ENST00000559488.5:c.774T>A

ENST00000560629.1:n.739T>A

ENST00000571680.1:c.774T>A

NM_000212.2:c.774T>A

Pathogenic

PVS1 PM3_Supporting PM2_Supporting PP4_Moderate

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.774T>A (p.Cys258Ter) is expected to introduce a premature termination codon 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) (Patient N, PMID: 26096001). 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 258 in exon 5/15. The resulting mRNA product is predicted to undergo nonsense mediated decay, leading to loss of normal protein function.

PM3_Supporting

This variant has been observed in homozygosity in one individual (Patient N, PMID: 26096001), sufficient to apply PM3_supporting.

PM2_Supporting

This is a rare variant not reported in control population databases, including gnomAD v2.1.1, gnomAD v3, PAGE, 1000 Genomes, and ESP, meeting the criterion to apply PM2_supporting.

PP4_Moderate

All requirements for PP4_moderate are met (Patient N, PMID: 26096001): history of bleeding and impaired aggregation to at least two agonists, but normal or only mildly reduced agglutination with ristocetin.

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