NM_000212.3:c.100C>T

CA8622852

Gene: ITGB3

Condition: Glanzmann's thrombasthenia

Inheritance Mode: Autosomal recessive inheritance

UUID: 7c5f28ee-e62f-4c7a-b19b-346462b4912f

Approved on: 2020-08-27

Published on: 2021-01-22

HGVS expressions

NM_000212.3:c.100C>T
NM_000212.2:c.100C>T
ENST00000559488.5:c.100C>T
ENST00000560629.1:n.65C>T
ENST00000571680.1:c.100C>T
NC_000017.11:g.47274439C>T
CM000679.2:g.47274439C>T
NC_000017.10:g.45351805C>T
CM000679.1:g.45351805C>T
NC_000017.9:g.42706804C>T
NG_008332.2:g.25598C>T

Pathogenic

• Met criteria codes: PM2_Supporting PVS1 PM3

• Not Met criteria codes: PP4

Expert Panel

Platelet Disorders VCEP

Criteria Specification Information

Evidence submitted by expert panel

Platelet Disorders VCEP

The ITGB3 nonsense variant NM_000212.3:c.100C>T (p.Arg34Ter) introduces a premature termination codon and the resulting mRNA product is predicted to undergo nonsense mediated decay, leading to loss of normal protein function. This variant has been observed in homozygosity in two individuals. Although flow cytometry demonstrated a marked reduction in protein surface expression consistent with Glanzmann's thrombasthenia (GT) in both patients, platelet aggregation information was not provided to determine if the individuals' phenotypes are specific for GT. This variant is rare in population databases. In summary, this variant meets criteria to be classified as pathogenic for GT. GT-specific criteria applied: PVS1, PM2_supporting, PM3.

Met criteria codes

• PM2_Supporting: This variant is rare in population databases, having been observed in 2/24960 alleles in the African population in gnomAD v2.1.1 and in 4/42048 alleles in the African population in gnomAD v3. The frequency of this variant is below the 1/10000 allele threshold required to apply PM2_supporting.
• PVS1: This variant introduces a termination codon at amino acid position 34 in exon 2/15. The resulting mRNA product is predicted to undergo nonsense mediated decay, leading to loss of normal protein function.
• PM3: This variant was reported in homozygosity in two individuals (CabGT-20 in PMID: 20020534 and the third patient described in PMID: 9450787). Each homozygous occurrence earns 0.5 points for a total of 1 point, sufficient to apply PM3.

Not Met criteria codes

• PP4: This variant was reported in homozygosity in two individuals (CabGT-20 in PMID: 20020534 and the third patient described in PMID: 9450787), however sufficient platelet aggregation information to meet PP4 was not provided.