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.444C>G (p.Tyr148Ter)

CA400021992

1684354 (ClinVar)

Gene: ITGB3 (HGNC:3690)

Condition: Glanzmann thrombasthenia (MONDO:0100326)

Inheritance Mode: Autosomal recessive inheritance

UUID: 397bd7bc-6990-4e72-9a0a-ba7e9bdbba9e

Approved on: 2024-04-16

Published on: 2024-04-16

HGVS expressions

NM_000212.3(ITGB3):c.444C>G (p.Tyr148Ter)

NM_000212.3:c.444C>G

NC_000017.11:g.47284525C>G

CM000679.2:g.47284525C>G

NC_000017.10:g.45361891C>G

CM000679.1:g.45361891C>G

NC_000017.9:g.42716890C>G

NG_008332.2:g.35684C>G

ENST00000696963.1:c.444C>G

ENST00000559488.7:c.444C>G

ENST00000559488.5:c.444C>G

ENST00000560629.1:c.409C>G

ENST00000571680.1:c.444C>G

NM_000212.2:c.444C>G

Pathogenic

PVS1 PM3_Supporting PM2_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

PDF

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Platelet Disorders VCEP

The c.444C>G (p.Tyr148Ter) variant in exon 4 is a nonsense variant predicted to cause a premature stop codon in biologically-relevant-exon 4 and is predicted to lead to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). The highest population minor allele frequency in gnomAD v4.0.0 is 0.000001799] (2/1112006 alleles) in the European (non-Finnish) population, which is lower than the ClinGen PD VCEP threshold (<0.0001; PM2_Supporting). This variant is reported in ClinVar (SCV002515562.1) in a homozygous Glanzmann thrombasthenia patient (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, PM3_Supporting and PM2_Supporting (VCEP specifications version 2; date of approval 04/16/2024.

PVS1

PM3_Supporting

One homozygous patient has been reported (SCV002515562.1) in the Gold Variants database (PM3_supporting).

PM2_Supporting

The highest population minor allele frequency in gnomAD v4.0.0 is 0.000001799] (2/1112006 alleles) in the European (non-Finnish) population, which is lower than the ClinGen PD VCEP threshold (<0.0001; PM2_Supporting).

PP4

This variant is reported in ClinVar in a Glanzmann thrombasthenia patient (ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology). No phenotypic information about this patient is provided, so PP4 could not be applied.

Curation History

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