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:c.2842-1G>C

CA399791378

Gene: ITGA2B

Condition: Glanzmann thrombasthenia

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 6169fea9-aeb2-40c5-9d98-6ff56d60a6b0

Approved on: 2022-10-06

Published on: 2022-12-07

HGVS expressions

NM_000419.5:c.2842-1G>C

NC_000017.11:g.44374761C>G

CM000679.2:g.44374761C>G

NC_000017.10:g.42452129C>G

CM000679.1:g.42452129C>G

NC_000017.9:g.39807655C>G

NG_008331.1:g.19745G>C

ENST00000262407.6:c.2842-1G>C

ENST00000648408.1:n.2273-1G>C

ENST00000262407.5:c.2842-1G>C

ENST00000587295.5:n.253+1072G>C

ENST00000592462.5:n.2352G>C

NM_000419.3:c.2842-1G>C

NM_000419.4:c.2842-1G>C

Uncertain Significance

PM2_Supporting PM3_Supporting PVS1_Moderate

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

The NM_000419.5(ITGA2B):c.2842-1G>C variant occurs within the canonical splice acceptor site of intron 27. It is predicted to cause skipping of biologically-relevant-exon 28, resulting in an in-frame deletion of 34 amino acids (Arg948_Gln981del), removing 3% of the protein (PVS1_moderate). The study of platelet GPIIb mRNA by RT-PCR confirmed an exon 28 skipping in this patient (PMID: 11798398). GT type I patient MMc (PMID: 11798398) is homozygous for this variant (PM3_supporting). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary, this variant meets the criteria to be classified as uncertain significance for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: PVS1_moderate, PM2_supporting, PM3_supporting.

PM2_Supporting

This variant is absent from gnomAD v2.1.1 (PM2_Supporting).

PM3_Supporting

MMc (PMID: 11798398) is homozygous for this variant (PM3_supporting)

PVS1_Moderate

PP4

Patient MMc (PMID: 11798398) was reported to have type I GT with a lack of GPIIb-GPIIIa at the platelet surface (by Western blot and flow cytometry). GT diagnosis was reportedly evoked on clinical presentation and platelet aggregation analysis. However no further details were available.

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