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]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computer assertion could be determined for this classification!

Variant: NM_000419.5(ITGA2B):c.3099A>T (p.Glu1033Asp)

CA290942825

627299 (ClinVar)

Gene: ITGA2B
Condition: Glanzmann thrombasthenia
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: 7338d3f7-38e1-488b-96ac-85ea02ef23a6
Approved on: 2024-05-02
Published on: 2024-05-03

HGVS expressions

NM_000419.5:c.3099A>T
NM_000419.5(ITGA2B):c.3099A>T (p.Glu1033Asp)
NC_000017.11:g.44372385T>A
CM000679.2:g.44372385T>A
NC_000017.10:g.42449753T>A
CM000679.1:g.42449753T>A
NC_000017.9:g.39805279T>A
NG_008331.1:g.22121A>T
ENST00000262407.6:c.3099A>T
ENST00000648408.1:c.2413A>T
ENST00000262407.5:c.3099A>T
ENST00000587295.5:c.292A>T
ENST00000588098.1:c.76A>T
NM_000419.3:c.3099A>T
NM_000419.4:c.3099A>T
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Uncertain Significance

Met criteria codes 2
PM2_Supporting BP4
Not Met criteria codes 2
PM3 PP4

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

PDF
Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Platelet Disorders VCEP
The missense variant c.3099A>T (p.Glu1033Asp) has been reported heterozygous in one patient (PMID: 31064749) however a second variant was not identified. Communication with the authors confirmed the patient had decreased platelet glycoprotein IIb-IIIa, abnormal bleeding, and impaired platelet aggregation with ADP, epinephrine, arachidonic acid, and collagen. The highest population minor allele frequency in gnomAD v4.0.0 is 0.00003334 (2/59980 alleles) in the Admixed American population, which is lower than the ClinGen PD VCEP threshold (<0.0001; PM2_Supporting). Computational predictors agree that this variant does not have a deleterious effect (REVEL score of 0.193; BP4). In summary, this variant meets criteria to be classified as uncertain significance for GT. GT-specific criteria applied: PM2_supporting, BP4.
Met criteria codes
PM2_Supporting
The highest population minor allele frequency in gnomAD v4.0.0 is 0.00003334 (2/59980 alleles) in the Admixed American population, which is lower than the ClinGen PD VCEP threshold (<0.0001; PM2_Supporting).
BP4
Computational predictors agree that this variant does not have a deleterious effect with a REVEL score of 0.193 (below the <0.25 threshold). And SpliceAI does not predict an impact on splicing.
Not Met criteria codes
PM3
One GT patient has been reported in ClinVar, by NIHR Bioresource Rare Diseases, heterozygous for this variant however the second variant was not indicated (patient TGP0212 from PMID: 31064749).
PP4
In PMID: 31064749 patient TGP0212 (heterozygous for this variant) is noted to have a disease of platelet function but no further information is provided. The variant is interpreted for Glanzmann thrombasthenia in ClinVar (SCV000899666.1) and communication with the authors confirmed the patient had decreased platelet glycoprotein IIb-IIIa, Abnormal bleeding, Impaired platelet aggregation with ADP, epinephrine, arachidonic acid, and collagen. insufficient information, no ristocetin agglutination reported
Curation History
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