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]
  • No ClinVar Id was directly found from the curated document
  • ClinVar Id was derived from the Allele Registry.
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC related information was provided by the message!
  • No CSPEC computed assertion could be determined for this classification!
  • See Evidence submitted by expert panel for details.

Variant: NM_000212.3:c.842A>C

CA400024802

1330335 (ClinVar)

Gene: ITGB3
Condition: Glanzmann thrombasthenia
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: ef63c97b-506b-488b-ae9e-6d8a57a0d655
Approved on: 2021-06-30
Published on: 2021-12-23

HGVS expressions

NM_000212.3:c.842A>C
NC_000017.11:g.47287134A>C
CM000679.2:g.47287134A>C
NC_000017.10:g.45364500A>C
CM000679.1:g.45364500A>C
NC_000017.9:g.42719499A>C
NG_008332.2:g.38293A>C
ENST00000696963.1:c.842A>C
ENST00000559488.7:c.842A>C
ENST00000559488.5:c.842A>C
ENST00000560629.1:c.807A>C
ENST00000571680.1:c.842A>C
NM_000212.2:c.842A>C
More

Likely Pathogenic

Met criteria codes 3
PP4_Strong PM2_Supporting PP3
Not Met criteria codes 1
PM3

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Platelet Disorders VCEP
The NM_000212.3(ITGB3):c.842A>C (p.His281Pro) missense variant has been identified in at least 1 probands, GT11 of PMID: 29675921 meeting the criteria for PP4_strong. This variant is absent from gnomAD v2.1.1 (PM2_Supporting). The computational predictor REVEL gives a score of 0.988, which predicts a damaging effect on ITGB3 function (PP3). In summary, this variant meets the criteria to be classified as Likely Pathogenic for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: PM2_supporting, PP3, PP4_strong. (VCEP specifications version 2; date of approval xx/xx/xxxx)
Met criteria codes
PP4_Strong
GT11 of PMID: 29675921 meets the criteria for PP4_strong; including mucocutaneous bleeding, impaired aggregation with all agonists except ristocetin, and reduced surface expression of αIIbβ3 measured by flow cytometry. ITGA2B and ITGB3 were sequenced across all exons and intron/exon boundaries.
PM2_Supporting
This variant is absent from gnomAD v2.1.1 (PM2_Supporting).
PP3
The computational predictor REVEL gives a score of 0.988, which is above the ClinGen PD VCEP threshold of >0.7 and predicts a damaging effect on ITGB3 function (PP3).
Not Met criteria codes
PM3
GT11 of PMID: 29675921 is compound heterozygous for His281Pro and Cys400Tyr (Classified Likely Pathogenic by the PD-VCEP). Confirmation of trans phase was not reported. 0.25pt
Curation History
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