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_000419.5:c.727del

CA915940727

Gene: ITGA2B (HGNC:3674)

Condition: Glanzmann thrombasthenia (MONDO:0100326)

Inheritance Mode: Autosomal recessive inheritance

UUID: 6840e950-97da-47e6-8562-173e19221ad9

Approved on: 2021-07-14

Published on: 2021-12-23

HGVS expressions

NM_000419.5:c.727del

NC_000017.11:g.44385021del

CM000679.2:g.44385021del

NC_000017.10:g.42462389del

CM000679.1:g.42462389del

NC_000017.9:g.39817915del

NG_008331.1:g.9486del

ENST00000262407.6:c.727del

ENST00000648408.1:n.158del

ENST00000262407.5:c.727del

ENST00000589645.5:n.178del

ENST00000591990.5:n.89del

ENST00000592075.5:n.96del

ENST00000592226.5:n.39+144del

ENST00000592253.5:n.235del

ENST00000592944.1:n.409del

NM_000419.3:c.727del

NM_000419.4:c.727del

Pathogenic

PM3_Supporting PP4_Moderate PM2_Supporting PVS1

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 ITGA2B frameshift variant NM_000419.5:c.727del (p.Leu243PhefsTer136) introduces a frameshift in exon 7 of 30 total exons and premature termination codon in exon 12. 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) (GT41, 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, PM3_Supporting, PP4_Moderate, and PM2_Supporting.

PM3_Supporting

This variant was reported in homozygosity in one individual (GT41 in PMID: 16463284), sufficient to apply PM3_Supporting.

PP4_Moderate

All requirements for PP4_Moderate are met (GT41 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.

PVS1

This variant introduces a frameshift in exon 7/30, leading to a premature termination codon in exon 12, and producing an mRNA product expected to be susceptible to nonsense mediated decay.

Curation History

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.