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]
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  • No ClinVar Id was directly found from the curated document
  • ClinVar Id was derived from the Allele Registry.

Variant: NM_000212.3:c.356G>A

CA8622925

996208 (ClinVar)

Gene: ITGB3
Condition: Glanzmann thrombasthenia
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: 97ec2eaf-2ba8-40ac-95e1-7e7ca00d472c

HGVS expressions

NM_000212.3:c.356G>A
NC_000017.11:g.47283544G>A
CM000679.2:g.47283544G>A
NC_000017.10:g.45360910G>A
CM000679.1:g.45360910G>A
NC_000017.9:g.42715909G>A
NG_008332.2:g.34703G>A
ENST00000559488.7:c.356G>A
ENST00000559488.5:c.356G>A
ENST00000560629.1:c.321G>A
ENST00000571680.1:c.356G>A
NM_000212.2:c.356G>A
NM_000212.3(ITGB3):c.356G>A (p.Arg119Gln)

Uncertain Significance

Met criteria codes 2
PP3 PP4_Strong
Not Met criteria codes 4
PS3 PM2 PM5 PM3

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
The NM_000212.3(ITGB3):c.356G>A variant predicts a missense change, Arg119Gln. It is reported at a frequency of 0.0001468 (11/74914 alleles) in the gnomAD v4.0.0 African/African-American population, above the <0.0001 threshold for PM2_Supporting. At least 4 GT patients (homozygous and compound heterozygous) with the variant have been reported in the literature (PMIDs: 19691478, 16463284, 25728920). The proband from PMID: 25728920 meets criteria for PP4_Strong including bleeding phenotype, abnormal platelet aggregation in response to >2 agonists and normal aggregation to ristocetin, reduced αIIbβ3 integrin expression on flow cytometry and full sequencing of ITGA2B and ITGB3 both genes. The variant has a REVEL score of 0.936, meeting criteria for PP3 (threshold: >0.7). In summary, there is insufficient evidence at this time to classify the Arg119Gln variant. GT-specific criteria met: PP3, PP4_strong.
Met criteria codes
PP3
REVEL score for Arg119Gln is 0.936 and meets criteria for PP3 (threshold: >0.7)
PP4_Strong
Proband from PMID: 25728920 meets criteria for PP4_Strong including bleeding phenotype, abnormal platelet aggregation in response to >2 agonists and normal aggregation to ristocetin, reduced αIIbβ3 integrin expression on flow cytometry and full sequencing of ITGA2B and ITGB3 both genes.
Not Met criteria codes
PS3
Evidence from PMID: 11861302 is noted for information but does not meet criteria for PS3.
PM2
The variant is reported at a frequency of 0.0001468 (11/74914 alleles) in the gnomAD v4.0.0 African/African-American population, above the <0.0001 threshold for PM2_Supporting.
PM5
Arg119Trp (c.355C>T) is a missense variant at the same residue. This variant is evaluated by the Platelet Disorders VCEP as a VUS. PM5 is not applicable at this time.
PM3
PM3 is not applied since PM2_Supporting is not met.
Approved on: 2023-11-02
Published on: 2023-11-03
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