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]

Variant: NM_000419.5(ITGA2B):c.1413C>T (p.Tyr471=)

CA8603102

698960 (ClinVar)

Gene: ITGA2B
Condition: Glanzmann thrombasthenia
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: ae373eb4-cc3b-4839-9733-ebd9a88c4236
Approved on: 2023-08-15
Published on: 2023-08-15

HGVS expressions

NM_000419.5:c.1413C>T
NM_000419.5(ITGA2B):c.1413C>T (p.Tyr471=)
NC_000017.11:g.44380626G>A
CM000679.2:g.44380626G>A
NC_000017.10:g.42457994G>A
CM000679.1:g.42457994G>A
NC_000017.9:g.39813520G>A
NG_008331.1:g.13880C>T
ENST00000262407.6:c.1413C>T
ENST00000648408.1:n.844C>T
ENST00000262407.5:c.1413C>T
ENST00000592226.5:n.886C>T
ENST00000592462.5:n.208C>T
NM_000419.3:c.1413C>T
NM_000419.4:c.1413C>T
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Likely Benign

Met criteria codes 2
BP7 BP4
Not Met criteria codes 2
PM2 BS1

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_000419.5(ITGA2B):c.1413C>T (p.Tyr471=), no individuals with Glanzmann Thrombasthenia were reported with the variant. The variant has a high minor allele frequency of 0.0005513 (11/19954 alleles) based off the East Asian population, which does not meet threshold for PM2_supporting or BS1. In silico predictor spliceAI revealed that the synonymous mutation is not expected to impact splicing and a PhyloP score of -1.38 shows that the nucleotide position is not highly conserved (BP4, BP7). In summary, this variant meets the criteria to be classified as Likely Benign for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: BP4 and BP7 (PD VCEP specifications version 2.1).
Met criteria codes
BP7
The c.1413C>T (p.Tyr471=) variant is a synonymous 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 -1.38 (BP7).
BP4
The c.1413C>T (p.Tyr471=) variant is a synonymous variant that is not predicted by SpliceAI to impact splicing (BP4).
Not Met criteria codes
PM2
The highest population minor allele frequency in gnomAD v2.1.1 is 0.0005513 (11/19954 alleles) in the East Asian population. This intermediate allele frequency is lower than the ClinGen PD VCEP threshold (>0.00158) for BS1 but higher than the threshold (<0.0001) for PM2_Supporting.
BS1
The highest population minor allele frequency in gnomAD v2.1.1 is 0.0005513 (11/19954 alleles) in the East Asian population. This intermediate allele frequency is lower than the ClinGen PD VCEP threshold (>0.00158) for BS1 but higher than the threshold (<0.0001) for PM2_Supporting.
Curation History
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