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_000419.5(ITGA2B):c.2188-7C>G

CA8602787

256039 (ClinVar)

Gene: ITGA2B
Condition: Glanzmann thrombasthenia
Inheritance Mode: Autosomal recessive inheritance
UUID: 945e65fa-09e6-4534-8741-f60d3c1168e2
Approved on: 2023-09-07
Published on: 2023-09-21

HGVS expressions

NM_000419.5:c.2188-7C>G
NM_000419.5(ITGA2B):c.2188-7C>G
NC_000017.11:g.44377095G>C
CM000679.2:g.44377095G>C
NC_000017.10:g.42454463G>C
CM000679.1:g.42454463G>C
NC_000017.9:g.39809989G>C
NG_008331.1:g.17411C>G
ENST00000262407.6:c.2188-7C>G
ENST00000648408.1:c.1619-7C>G
ENST00000262407.5:c.2188-7C>G
ENST00000592462.5:n.983-7C>G
NM_000419.3:c.2188-7C>G
NM_000419.4:c.2188-7C>G

Benign

Met criteria codes 3
BP7 BP4 BA1

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 intronic variant NM_000419.5(ITGA2B):c.2188-7C>G, no individuals with Glanzmann Thrombasthenia were reported with the variant. The variant has a high minor allele frequency of 0.4311 (6420/14892 alleles) in the East Asian population, which is higher than the ClinGen PD VCEP threshold (>0.0024), and therefore meets benign criterion (BA1). In silico predictor spliceAI revealed that the intronic mutation is not expected to impact splicing and a PhyloP score of 0.287 shows that the nucleotide position is not highly conserved (BP4, BP7). In summary, this variant meets the criteria to be classified as Benign for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: BA1, BP4 and BP7 (PD VCEP specifications version 2.1).
Met criteria codes
BP7
The c.2188-7C>G variant is a intronic variant that is not predicted by SpliceAI to impact splicing. In addition, it occurs at a nucleotide that is not conserved as shown by phyloP score of 0.287 (BP7).
BP4
The c.2188-7C>G variant is an intronic variant that is not predicted by SpliceAI to impact splicing (BP4).
BA1
The highest population minor allele frequency in gnomAD v2.1.1 is 0.4311 (6420/14892 alleles) in the East Asian population, which is higher than the ClinGen PD VCEP threshold (>0.0024), and therefore meets this criterion (BA1).
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