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]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computer assertion could be determined for this classification!

Variant: NM_000212.3(ITGB3):c.1309G>T (p.Glu437Ter)

CA8623244

1695377 (ClinVar)

Gene: ITGB3 (HGNC:3690)
Condition: Glanzmann thrombasthenia (MONDO:0100326)
Inheritance Mode: Autosomal recessive inheritance
UUID: 6e67cd67-37d2-4bd3-b64e-97e9f51a835e
Approved on: 2024-04-16
Published on: 2024-04-16

HGVS expressions

NM_000212.3(ITGB3):c.1309G>T (p.Glu437Ter)
NM_000212.3:c.1309G>T
NC_000017.11:g.47292187G>T
CM000679.2:g.47292187G>T
NC_000017.10:g.45369553G>T
CM000679.1:g.45369553G>T
NC_000017.9:g.42724552G>T
NG_008332.2:g.43346G>T
ENST00000696963.1:c.1309G>T
ENST00000559488.7:c.1309G>T
ENST00000559488.5:c.1309G>T
ENST00000560629.1:c.1274G>T
NM_000212.2:c.1309G>T
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Pathogenic

Met criteria codes 3
PM3_Supporting PM2_Supporting PVS1
Not Met criteria codes 2
PP4 BS2

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

PDF
Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Platelet Disorders VCEP
The c.1309G>T (p.Glu437Ter) variant in exon 10 is a nonsense variant predicted to cause a premature stop codon in biologically-relevant-exon 10 and is predicted to lead to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). The highest population minor allele frequency in gnomAD v4.0.0 is 0.00002319 (2/86254 alleles) in the South Asian population, which is lower than the ClinGen PD VCEP threshold (<0.0001; PM2_Supporting). This variant is reported in ClinVar (SCV002546491.1) in a homozygous Glanzmann thrombasthenia patient (PM3_Supporting). In summary, this variant meets the criteria to be classified as Pathogenic for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: PVS1, PM3_Supporting, and PM2_Supporting (VCEP specifications version 2; date of approval 04/16/2024).
Met criteria codes
PM3_Supporting
One homozygous patient has been reported (SCV002546491.1) in the Gold Variants database (PM3_supporting).
PM2_Supporting
The highest population minor allele frequency in gnomAD v4.0.0 is 0.00002319 (2/86254 alleles) in the South Asian population, which is lower than the ClinGen PD VCEP threshold (<0.0001; PM2_Supporting).
PVS1
The c.1309G>T (p.Glu437Ter) variant in exon 10 is a nonsense variant predicted to cause a premature stop codon in biologically-relevant-exon 10 and is predicted to lead to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1).
Not Met criteria codes
PP4
Variant is reported in a GT case in ClinVar (ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology). No phenotypic details about the patient are provided, so PP4 cannot be applied.
BS2
A homozygous patient is reported (PMID: 29143464) but not asserted to have GT, they have a platelet count of 208x10^9/L and MPV of 12.7 fl. No aggregation or bleeding information is provided.
Curation History
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