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.1303G>T

CA400028645

Gene: ITGB3 (HGNC:3690)

Condition: Glanzmann thrombasthenia (MONDO:0100326)

Inheritance Mode: Autosomal recessive inheritance

UUID: 50c6d852-43dc-45fe-99cd-7eea271ae7d4

Approved on: 2022-11-15

Published on: 2022-12-07

HGVS expressions

NM_000212.3:c.1303G>T

NC_000017.11:g.47292181G>T

CM000679.2:g.47292181G>T

NC_000017.10:g.45369547G>T

CM000679.1:g.45369547G>T

NC_000017.9:g.42724546G>T

NG_008332.2:g.43340G>T

ENST00000559488.7:c.1303G>T

ENST00000559488.5:c.1303G>T

ENST00000560629.1:n.1268G>T

NM_000212.2:c.1303G>T

Pathogenic

PM2_Supporting PVS1 PM3_Supporting

PP4

Evidence Links 0

Expert Panel

Platelet Disorders VCEP

Criteria Specification Information

Criteria Specification: ClinGen Platelet Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 2.1

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Platelet Disorders VCEP

NM_000212.3(ITGB3):c.1303G>T (p.Glu435Ter) found in a homozygous proband (PMID:31029159; PM3_supporting) causes a premature stop codon at exon 10/15 and is predicted to undergo nonsense mediated decay (PVS1). The mutation was not found in gnomAD v2.1.1 (PM2_supporting). In conclusion the criteria PVS1, PM2_supporting, and PM3_supporting were applied to reach a classification of pathogenic.

PM2_Supporting

This variant is absent from gnomAD v[2.1.1] (PM2_Supporting).

PVS1

The c.1303G>T (p.Glu435Ter) variant in exon 10 is a nonsense variant predicted to cause a premature stop codon in biologically-relevant-exon 10/15 and is predicted to lead to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1).

PM3_Supporting

This variant has been detected in at least 1 proband with Glanzmann Thrombasthenia. One proband was homozygous for the variant, confirmed via paternal testing (PMID: 31029159). Total points: .5 (PM3_supporting).

PP4

At least one patient (Patient 4 in PMID:31029159) with this variant displayed bleeding phenotypes including purpura, menorrhagia, bruising susceptibility, and epistaxis, however, there was no platelet aggregation testing information associated with this individual (Not Met).

Curation History

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