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]

Link to SEPIO compliant JSON-LD document

Variant: NM_000212.3(ITGB3):c.273G>A (p.Glu91=)

CA8622907

751827 (ClinVar)

Gene: ITGB3

Condition: Glanzmann thrombasthenia

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 7fd0d2ea-a806-436c-a172-c3e5f2345fc1

HGVS expressions

NM_000212.3:c.273G>A

NM_000212.3(ITGB3):c.273G>A (p.Glu91=)

NC_000017.11:g.47283461G>A

CM000679.2:g.47283461G>A

NC_000017.10:g.45360827G>A

CM000679.1:g.45360827G>A

NC_000017.9:g.42715826G>A

NG_008332.2:g.34620G>A

ENST00000559488.7:c.273G>A

ENST00000559488.5:c.273G>A

ENST00000560629.1:n.238G>A

ENST00000571680.1:c.273G>A

NM_000212.2:c.273G>A

Uncertain Significance

PM2_Supporting

BP7

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

After a comprehensive literature search of the synonymous variant NM_000212.3(ITGB3):c.273G>A (p.Glu91=), no individuals with Glanzmann thrombasthenia were reported with the variant. The variant has a minor allele frequency of 0.00006 (2/35438 alleles) in the Latino/Admixed American population in gnomAD, which meets our threshold criteria for PM2_Supporting. In silico predictor SpliceAI revealed that the synonymous mutation is not expected to impact splicing but a PhyloP score of 2.318 shows that the nucleotide position is highly conserved. Due to insufficient evidence, this variant is classified as a variant of unknown significance for Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD-VCEP: PM2_Supporting (PD VCEP specifications version 2.1).

PM2_Supporting

The highest population minor allele frequency in gnomAD v2.1.1 is 0.00006 (2/35438 alleles) in the Latino/Admixed American population, which is lower than the ClinGen PD VCEP threshold (<0.0001; PM2_Supporting).

BP7

The c.273G>A (p.Glu91=) variant is a synonymous variant that is not predicted by SpliceAI to impact splicing, however it is highly conserved as shown by PhyloP score of 2.318.

Approved on: 2023-08-15

Published on: 2023-08-15

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