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_000419.5(ITGA2B):c.2507G>C (p.Gly836Ala)

CA399795012

627284 (ClinVar)

Gene: ITGA2B
Condition: Glanzmann thrombasthenia
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: e8d529b9-a3b6-471a-a57b-1b42505a02c0
Approved on: 2024-05-02
Published on: 2024-05-03

HGVS expressions

NM_000419.5:c.2507G>C
NM_000419.5(ITGA2B):c.2507G>C (p.Gly836Ala)
NC_000017.11:g.44375927C>G
CM000679.2:g.44375927C>G
NC_000017.10:g.42453295C>G
CM000679.1:g.42453295C>G
NC_000017.9:g.39808821C>G
NG_008331.1:g.18579G>C
ENST00000262407.6:c.2507G>C
ENST00000648408.1:c.1938G>C
ENST00000262407.5:c.2507G>C
ENST00000587295.5:c.159G>C
ENST00000592462.5:n.1302G>C
NM_000419.3:c.2507G>C
NM_000419.4:c.2507G>C
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Uncertain Significance

Met criteria codes 3
PM3_Supporting PM2_Supporting BP4
Not Met criteria codes 1
PP4

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.2507G>C variant in ITGA2B is a missense variant predicted to cause substitution of Glycine by Alanine at amino acid 836 (p.Gly836Ala). This variant is absent from gnomAD v4.0.0 (PM2_Supporting). The computational predictor REVEL gives a score of 0.152, which is below the ClinGen PD VCEP threshold of <0.25 and predicts no damaging effect on ITGA2B function (BP4). A male patient is reported homozygous this variant (TGP0413 in PMID: 31064749; PM3_Supporting) however, his phenotype is not detailed enough to apply PP4 as specified by the PD VCEP. Due to conflicting evidence, this variant is classified as a variant of unknown significance for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD-VCEP: PM2_Supporting, PM3_Supporting and BP4 (VCEP specifications version 2).
Met criteria codes
PM3_Supporting
GT patient TGP0413 (PMID: 31064749) is homozygous for this variant.
PM2_Supporting
This variant is absent from gnomAD v4.0.0 (PM2_Supporting).
BP4
The computational predictor REVEL gives a score of 0.152, which is below the ClinGen PD VCEP threshold of <0.25 and predicts no damaging effect on ITGA2B function (BP4). And SpliceAI does not predict a significant impact on splicing.
Not Met criteria codes
PP4
The patient in ClinVar and PMID: 31064749 had decreased platelet glycoprotein IIb-IIIa, abnormal bleeding, impaired platelet aggregation with ADP, epinephrine, arachidonic acid, and collagen. Insufficient information, no Ristocetin agglutination results reported.
Curation History
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