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(ITGB3):c.55dup (p.Ala19fs)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA915940803

627094 (ClinVar)

Gene: ITGB3

Condition: Glanzmann thrombasthenia

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 6ee78cc1-ae82-4306-bc34-c46e44aa76c0

Approved on: 2023-03-21

Published on: 2023-03-21

HGVS expressions

NM_000212.3:c.55dup

NM_000212.3(ITGB3):c.55dup (p.Ala19fs)

NC_000017.11:g.47253916dup

CM000679.2:g.47253916dup

NC_000017.10:g.45331282dup

CM000679.1:g.45331282dup

NC_000017.9:g.42686281dup

NG_008332.2:g.5075dup

ENST00000559488.7:c.55dup

ENST00000559488.5:c.55dup

ENST00000560629.1:n.20dup

ENST00000571680.1:c.55dup

NM_000212.2:c.55dup

Pathogenic

PM3_Supporting PM2_Supporting PVS1

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.55dup (p.Ala19GlyfsTer?) is a frameshift variant in exon 1 predicted to cause a premature stop codon in biologically-relevant-exon 2/15 and is predicted to lead to nonsense mediated decay in a gene in which loss-of-function is an established mechanism (PVS1). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). Patient TGP0454, PMID:31064749, is reported to have a clinical diagnosis of GT type 1 and is homozygous for this variant (PM3_supporting). In summary, this variant meets the criteria to be classified as Pathogenic for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: PVS1, PM2_supporting, PM3_supporting (VCEP specifications version 2.1).

PM3_Supporting

This variant has been detected in at least 1 proband with type 1 Glanzmann thrombasthenia. One probands was homozygous for the variant (PMID:31064749, Total points: .5 points (PM3_supporting).

PM2_Supporting

Variant is absent from gnomAD (PM2_supporting).

PVS1

The NM_000212.3(ITGB3):c.55dup p.Ala19GlyfsTer? variant in exon 1 is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon 2/15 and is predicted to lead to nonsense mediated decay in a gene in which loss-of-function is an established mechanism (PVS1)

PP4

PP4_moderate was not met given there was no platelet aggregation data or specific phenotypes reported with this patient.

Curation History

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