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]

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Variant: NM_000419.5(ITGA2B):c.2094+2T>C

CA399799489

458368 (ClinVar)

Gene: ITGA2B

Condition: Glanzmann's thrombasthenia

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 68d65d3d-65f0-478d-a0b8-8f26afd05413

Approved on: 2021-05-07

Published on: 2021-08-20

HGVS expressions

NM_000419.5:c.2094+2T>C

NM_000419.5(ITGA2B):c.2094+2T>C

ENST00000262407.6:c.2094+2T>C

ENST00000648408.1:n.1525+2T>C

ENST00000262407.5:c.2094+2T>C

ENST00000592462.5:n.889+2T>C

NM_000419.3:c.2094+2T>C

NM_000419.4:c.2094+2T>C

NC_000017.11:g.44378360A>G

CM000679.2:g.44378360A>G

NC_000017.10:g.42455728A>G

CM000679.1:g.42455728A>G

NC_000017.9:g.39811254A>G

NG_008331.1:g.16146T>C

Pathogenic

PM3_Supporting PVS1 PM2_Supporting

PP4

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 NM_000419.5(ITGA2B):c.2094+2T>C splice variant is predicted to cause skipping of exon 20, introducing 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 reported to have Glanzmann's thrombasthenia (GT), however sufficient phenotype information was not provided to determine if the individual's phenotype is specific for GT. This variant is absent from population databases, including gnomAD. In summary, this variant meets criteria to be classified as pathogenic for GT. GT-specific criteria applied: PVS1, PM2_Supporting, and PM3_supporting.

PM3_Supporting

One homozygous GT patient was reported in ClinVar by Invitae. 0.5pt

PVS1

Splice variant c.2094+2T>C is predicted to cause skipping of exon 20, causing a frameshift resulting in a premature stop codon in exon 21 of 30. This is expected to result in NMD.

PM2_Supporting

This variant is absent from all population cohorts in gnomAD, ExAC, 1000 Genomes, and ESP.

PP4

One patient was reported in ClinVar by Invitae, however insufficient information was provided to apply PP4.

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