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.3061-6C>G

CA915940801

Gene: ITGA2B

Condition: Glanzmann thrombasthenia

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: f79d61cd-e2f7-45fb-90ce-95de0a59f3d4

HGVS expressions

NM_000419.5:c.3061-6C>G

NC_000017.11:g.44372429G>C

CM000679.2:g.44372429G>C

NC_000017.10:g.42449797G>C

CM000679.1:g.42449797G>C

NC_000017.9:g.39805323G>C

NG_008331.1:g.22077C>G

ENST00000262407.6:c.3061-6C>G

ENST00000648408.1:n.2375-6C>G

ENST00000262407.5:c.3061-6C>G

ENST00000587295.5:n.254-6C>G

ENST00000588098.1:n.38-6C>G

NM_000419.3:c.3061-6C>G

NM_000419.4:c.3061-6C>G

Uncertain Significance

PM2_Supporting PM3_Supporting PM4

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.3061-6C>G intronic variant is predicted by varSEAK (class 5) to cause loss of the canonical splice acceptor site. In PMID: 11798398, the authors found that study of platelet mRNA showed the addition of six bases between exons 29 and 30, resulting in an insertion of two amino acids (Lys989_Val990insProGln; PM4). GT type I patient TG (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: PM4, PM2_supporting, PM3_supporting.

PM2_Supporting

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

PM3_Supporting

TG (PMID: 11798398) is homozygous for this variant 0.5pt

PM4

The NM_000419.5:c.3061-6C>G intronic variant is predicted by varSEAK (class 5) to cause loss of the canonical splice acceptor site. In PMID: 11798398 the authors found that study of platelet mRNA showed the addition of six bases between exons 29 and 30, resulting in an insertion of two amino acids (Lys989_Val990insProGln).

PP4

Patient TG (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.

Approved on: 2022-10-06

Published on: 2022-12-07

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