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
  • ClinVar Id was derived from the Allele Registry.

Variant: NM_000419.4:c.3115_3119dup

CA915940262

952996 (ClinVar)

Gene: ITGA2B
Condition: Glanzmann thrombasthenia
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: 98612d26-4b31-40f1-8b8c-89c0873ab2a5
Approved on: 2023-08-15
Published on: 2023-09-21

HGVS expressions

NM_000419.4:c.3115_3119dup
NC_000017.11:g.44372366_44372370dup
CM000679.2:g.44372366_44372370dup
NC_000017.10:g.42449734_42449738dup
CM000679.1:g.42449734_42449738dup
NC_000017.9:g.39805260_39805264dup
NG_008331.1:g.22137_22141dup
ENST00000262407.6:c.3115_3119dup
ENST00000648408.1:c.2429_2433dup
ENST00000262407.5:c.3115_3119dup
ENST00000587295.5:c.308_312dup
ENST00000588098.1:c.92_96dup
NM_000419.3:c.3115_3119dup
NM_000419.5:c.3115_3119dup
NM_000419.5(ITGA2B):c.3115_3119dup (p.Ter1040TrpextTer?)
More

Likely Pathogenic

Met criteria codes 4
PM3_Supporting PM4 PM2_Supporting PP4_Moderate

Evidence Links 1

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 stop loss NM_000419.5(ITGA2B):c.3115_3119dup variant causes Ter1040Trp and extension of the protein by 92 amino acids (PM4). It has been observed in the homozygous state in one patient with a phenotype highly specific to GT, including mucocutaneous bleeding, impaired aggregation with all agonists except ristocetin, and <5% surface expression of αIIbβ3 measured by flow cytometry (PMID: 19691478; PP4_moderate, PM3_supporting). This variant is absent from gnomADv2.1.1 (PM2_Supporting). In summary, this variant meets the criteria to be classified as likely pathogenic for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: PM2_supporting, PM4, PP4_moderate, PM3_supporting (PD VCEP specifications version 2.1).
Met criteria codes
PM3_Supporting
This variant has been observed in one homozygous patient (PMID: 19691478). 0.5pt
Patient 51 is homozygous for this variant, as recorded in the GT database. PubMed:19691478
PM4
The variant occurs in exon 30 of 30 and causes a stop loss with elongation of the protein by 92 amino acids until a new stop codon is reached.
PM2_Supporting
This variant is absent from gnomAD, ExAC and 1000 Genomes.
PP4_Moderate
One patient has been described with this variant who meets the criteria for PP4, including mucocutaneous bleeding, impaired aggregation with all agonists except ristocetin, and <5% surface expression of αIIbβ3 measured by flow cytometry.
Patient GT51 had a history of mucocutaneous bleeding (including gum bleeding and menorrhagia), absent or reduced aggregation in response to ADP, ADR, AA and collagen and normal aggregation with ristocetin, normal platelet size, normal platelet count and no other platelet function defects. Flow cytometry for surface expression characterized the patient as Type I GT with <5% expression. PubMed:19691478
Curation History
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