Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • No ClinVar Id was directly found from the curated document

Variant: NM_000419.5:c.3061-1G>A

CA399787972

Gene: ITGA2B
Condition: Glanzmann thrombasthenia
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: c266c29a-548a-4279-913f-2f50beec1f0d
Approved on: 2022-08-05
Published on: 2022-12-07

HGVS expressions

NM_000419.5:c.3061-1G>A
NC_000017.11:g.44372424C>T
CM000679.2:g.44372424C>T
NC_000017.10:g.42449792C>T
CM000679.1:g.42449792C>T
NC_000017.9:g.39805318C>T
NG_008331.1:g.22082G>A
ENST00000262407.6:c.3061-1G>A
ENST00000648408.1:n.2375-1G>A
ENST00000262407.5:c.3061-1G>A
ENST00000587295.5:n.254-1G>A
ENST00000588098.1:n.38-1G>A
NM_000419.3:c.3061-1G>A
NM_000419.4:c.3061-1G>A
More

Pathogenic

Met criteria codes 4
PM3_Supporting PVS1_Strong PM2_Supporting PP4_Strong

Evidence Links 0

Expert Panel

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.3061-1G>A occurs within the canonical splice acceptor site of intron 29. It is predicted to cause skipping of biologically-relevant-exon 29, resulting in the in-frame deletion of 39 amino acids (3.7% of the protein) of the transmembrane region, which is considered a critical region by the PD-EP (PVS1_strong). At least one patient (GT31 in PMID: 25728920) with this variant displayed mucocutaneous bleeding and impaired aggregation with all agonists except ristocetin, which is highly specific for Glanzmann thrombasthenia. Additionally, αIIbβ3 surface expression was reduced to <5%, as measured by flow cytometry (PP4_strong). GT31 is compound heterozygous for c.1771dup (classified Pathogenic by the PD-EP) and c.3061-1G>A (PM3_supporting). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary this variant meets 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_strong, PP4_strong, PM2_supporting, PM3_supporting. (VCEP specifications version 2.1).
Met criteria codes
PM3_Supporting
GT31 (PMID: 25728920) is compound heterozygous for c.1771dup (classified Pathogenic by the PD-EP) and c.3061-1G>A. Confirmation of trans phase was not reported. (0.5pt; PM3_supporting)
PVS1_Strong
The NM_000419.5:c.3061-1G>A occurs within the canonical splice acceptor site of intron 29. It is predicted to cause skipping of biologically-relevant-exon 29, resulting in the in-frame deletion of 39 amino acids (3.7% of the protein) of the transmembrane region, which is considered a critical region by the PD-EP (PVS1_strong).
PM2_Supporting
This variant is absent from gnomAD v2.1.1 (PM2_Supporting).
PP4_Strong
At least one patient (GT31 in PMID: 25728920) with this variant displayed mucocutaneous bleeding and impaired aggregation with all agonists except ristocetin, which is highly specific for Glanzmann thrombasthenia. Additionally, αIIbβ3 surface expression was reduced to <5%, as measured by flow cytometry. ITGA2B and ITGB3 were sequenced across all exons and intron/exon boundaries. (PP4_strong)
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.
¤ Powered by BCM's Genboree.