Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_000212.3:c.122_125dup

CA915940804

953030 (ClinVar)

Gene: ITGB3 (HGNC:3690)

Condition: Glanzmann's thrombasthenia (MONDO:0010119)

Inheritance Mode: Autosomal recessive inheritance

UUID: f6a5ee90-18f2-4c37-8ef2-253611169962

Approved on: 2020-06-04

Published on: 2021-01-23

HGVS expressions

NM_000212.3:c.122_125dup

NC_000017.11:g.47274461_47274464dup

CM000679.2:g.47274461_47274464dup

NC_000017.10:g.45351827_45351830dup

CM000679.1:g.45351827_45351830dup

NC_000017.9:g.42706826_42706829dup

NG_008332.2:g.25620_25623dup

NM_000212.2:c.122_125dup

ENST00000559488.5:c.122_125dup

ENST00000560629.1:n.87_90dup

ENST00000571680.1:c.122_125dup

Pathogenic

PM3_Supporting PVS1 PM2_Supporting

PP4

Evidence Links 0

Expert Panel

Platelet Disorders VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Platelet Disorders VCEP

The NM_000212.2:c.122_125dup variant results in premature termination of translation at Cys42 in exon 2/15. The resulting transcript is predicted to undergo NMD. The variant is absent from all population databases including gnomAD. The variant is reported in one homozygous individual who does not meet criteria for PP4 (PMID: 12353082). In summary, based on the evidence available at this time, the variant is classified as pathogenic. GT-specific criteria applied: PVS1, PM2_Supporting, PM3_Supporting.

PM3_Supporting

One GT patient has been identified with this homozygous variant in PMID: 12353082 (Patient 2).

PVS1

The c.122_125dup variant immediately generates the Cys42Ter premature stop codon in exon 2 of 15. This is predicted to result in NMD.

PM2_Supporting

This variant is absent from all population cohorts in gnomAD, ExAC, 1000 Genomes, and ESP.

PP4

One patient has been identified with this variant in PMID: 12353082. Patient 2 was diagnosed with GT based on absence of platelet aggregation in response to ADP and <1% of normal levels of platelet surface expression measured by radio-electroimmunoassay. Additionally, under nonreduced immunoblot conditions, beta3 subunits were undetectable. This patient does not meet PP4 because only one agonist was reported with impaired aggregation and ristocetin response was not reported (although it was noted to be normal in the GT database), and surface expression was not measured by either flow cytometry or Western blot.

Curation History

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.