The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]


Variant: NM_000212.3(ITGB3):c.882T>C (p.Pro294=)

CA8623073

255541 (ClinVar)

Gene: ITGB3
Condition: Glanzmann thrombasthenia
Inheritance Mode: Autosomal recessive inheritance
UUID: 0bb4a9cb-8aa6-4fb7-ba86-673dfbdc4a7e
Approved on: 2022-12-01
Published on: 2022-12-07

HGVS expressions

NM_000212.3:c.882T>C
NM_000212.3(ITGB3):c.882T>C (p.Pro294=)
NC_000017.11:g.47287174T>C
CM000679.2:g.47287174T>C
NC_000017.10:g.45364540T>C
CM000679.1:g.45364540T>C
NC_000017.9:g.42719539T>C
NG_008332.2:g.38333T>C
ENST00000559488.7:c.882T>C
ENST00000559488.5:c.882T>C
ENST00000560629.1:n.847T>C
ENST00000571680.1:c.882T>C
NM_000212.2:c.882T>C
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Benign

Met criteria codes 3
BA1 BP7 BP4

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
After a comprehensive literature search of the synonymous variant NM_000212.3(ITGB3):c.882T>C (p.Pro294=), no individuals with Glanzmann thrombasthenia were reported with the variant. Moreover, the variant has a minor allele frequency of 0.2463 (4912/19940 alleles) in gnomAD, found in the East Asian population, which is considerably higher than the expected frequency of the disease (BA1). In Silico predictor spliceAI revealed that the synonymous mutation is not expected to impact splicing at a nucleotide site that is not highly conserved. In conclusion the criteria BA1, BP4, and BP7 were applied to reach a classification of benign.
Met criteria codes
BA1
The highest population minor allele frequency in gnomAD v2.1.1 is 0.2463 (4912/19940 alleles) in the East Asian population, which is higher than the ClinGen PD VCEP threshold (>0.0024), and therefore meets this criterion (BA1).
BP7
The c.882T>C (p.Pro294=) variant is a synonymous variant that is not predicted by SpliceAI to impact splicing. In addition, it occurs at a nucleotide that is not highly conserved as shown by phyloP score of 1.244 (BP7).
BP4
The NM_000212.3(ITGB3):c.882T>C (p.Pro294=) variant is a synonymous variant that is not predicted by SpliceAI to impact splicing (BP4).
Curation History
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