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]
Link to SEPIO compliant JSON-LD document
  • No ClinVar Id was directly found from the curated document

Variant: NM_000212.3:c.330_336del

CA915940806

Gene: ITGB3
Condition: Glanzmann thrombasthenia
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: e609a61c-0e59-4ab2-a6f2-4841f790181f

HGVS expressions

NM_000212.3:c.330_336del
NC_000017.11:g.47283518_47283524del
CM000679.2:g.47283518_47283524del
NC_000017.10:g.45360884_45360890del
CM000679.1:g.45360884_45360890del
NC_000017.9:g.42715883_42715889del
NG_008332.2:g.34677_34683del
ENST00000559488.7:c.330_336del
ENST00000559488.5:c.330_336del
ENST00000560629.1:n.295_301del
ENST00000571680.1:c.330_336del
NM_000212.2:c.330_336del

Pathogenic

Met criteria codes 4
PM2_Supporting PVS1 PM3_Supporting PP4_Moderate

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
NM_000212.3(ITGB3):c.330_336del (p.Ser110ArgfsTer32) frameshift variant in exon 3 is predicted to cause a premature stop codon in biologically-relevant-exon 4/15 and is predicted to lead to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). At least one patient (UPN 10 in PMID: 16879215) with this variant displayed mucocutaneous bleeding and impaired aggregation with all agonists except ristocetin, which is highly specific for Glanzmann thrombasthenia (PP4_moderate). Additionally, αIIbβ3 surface expression was reduced to 3%, as measured by flow cytometry. UPN 10 is homozygous for this variant (PM3_supporting; PMID: 16879215). This variant is absent from gnomAD v2.1.1 (PM2_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, PM2_supporting, PM3_supporting, PP4_moderate.
Met criteria codes
PM2_Supporting
This variant is absent from gnomAD v2.1.1 (PM2_Supporting).
PVS1
NM_000212.3(ITGB3):c.330_336del (p.Ser110ArgfsTer32) frameshift variant in exon 3 is predicted to cause a premature stop codon in biologically-relevant-exon 4/15 and is predicted to lead to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). RT-PCR analysis revealed a product of about the size of the normal control cDNA product, consistent with normal splicing, sequencing of which confirmed the 7-bp deletion.
PM3_Supporting
UPN 10 is homozygous for this variant (PM3_supporting; PMID: 16879215).
PP4_Moderate
At least one patient (UPN 10 in PMID: 16879215) with this variant displayed mucocutaneous bleeding and impaired aggregation with all agonists except ristocetin, which is highly specific for Glanzmann thrombasthenia (PP4_moderate). Additionally, αIIbβ3 surface expression was reduced to 3%, as measured by flow cytometry. However, ITGA2B and ITGB3 were not sequenced across all exons and intron/exon boundaries.
Approved on: 2022-10-06
Published on: 2022-12-07
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.