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!
  • No Criteria Specification was provided in the publication event for the variant classifaction.
  • The Criteria Specification shown below is a best-estimate based on the VCEP, gene, disease, and publication date.

Variant: NM_000212.2:c.2113del

CA8623443

953051 (ClinVar)

Gene: ITGB3 (HGNC:3690)
Condition: Glanzmann's thrombasthenia (MONDO:0010119)
Inheritance Mode: Autosomal recessive inheritance
UUID: 655285f6-312a-42c6-a721-9f9a8fa8843f
Approved on: 2020-09-06
Published on: 2021-01-28

HGVS expressions

NM_000212.2:c.2113del
NC_000017.11:g.47302819del
CM000679.2:g.47302819del
NC_000017.10:g.45380185del
CM000679.1:g.45380185del
NC_000017.9:g.42735184del
NG_008332.2:g.53978del
ENST00000696963.1:c.2113del
ENST00000559488.7:c.2113del
ENST00000559488.5:c.2113del
ENST00000560629.1:c.2078del
NM_000212.3:c.2113del
More

Pathogenic

Met criteria codes 5
PVS1 PP4_Strong PP1_Strong PM2_Supporting PM3

Evidence Links 3

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Platelet Disorders VCEP
The frameshift variant NM_000212.2:c.2113del results in the creation of a premature stop codon in exon 13 of 15, which is expected to result in NMD. It occurs at an extremely low allele frequency with a MAF of 0.0000932 in the East Asian population on gnomAD. It has been reported in at least 4 homozygotes and three compound heterozygous patient with a phenotype highly specific to GT, as well as at least 7 family members (PMIDs: 31088191, 30792900, 25728920). In summary, based on the available evidence at this time, the variant is classified as Pathogenic. GT-specific criteria applied: PVS1, PM2_Supporting, PM3, PP1_Strong, PP4_Strong.
Met criteria codes
PVS1
This frameshift variant occurs in exon 13 of 15 where it generates a premature stop codon, which is expected to result in NMD.
PP4_Strong
At least one proband been reported (PMID: 25728920) with this variant that 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.
PP1_Strong
There are a minimum of 7 segregations across 2 families with affected individuals homozygous for this variant (PMID: 30792900).
PM2_Supporting
This variant is at an extremely low frequency (below the <1/10,000 threshold) with an overall allele frequency from gnomAD of 0.000007955 and MAF of 0.0001087 (2/18,394 alleles) in the East Asian population of gnomADv2.1.1 plus an additional 3,052 East asian alleles not carrying the variant in gnomADv3 for an overall MAF of 0.0000932.
PM3
At least four homozygous probands have been reported (PMID: 30792900). An additional three compound heterozygotes have not been included here to avoid circularity.
PubMed:25728920
PubMed:30792900
PubMed:31088191
Curation History
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