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(ITGB3):c.197T>G (p.Leu66Arg)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA8622895

695335 (ClinVar)

Gene: ITGB3

Condition: Glanzmann's thrombasthenia

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: d9b94a86-212e-420f-98f5-7157dba80330

Approved on: 2021-03-05

Published on: 2021-08-20

HGVS expressions

NM_000212.3:c.197T>G

NM_000212.3(ITGB3):c.197T>G (p.Leu66Arg)

NC_000017.11:g.47283385T>G

CM000679.2:g.47283385T>G

NC_000017.10:g.45360751T>G

CM000679.1:g.45360751T>G

NC_000017.9:g.42715750T>G

NG_008332.2:g.34544T>G

ENST00000696963.1:c.197T>G

ENST00000559488.7:c.197T>G

ENST00000559488.5:c.197T>G

ENST00000560629.1:c.162T>G

ENST00000571680.1:c.197T>G

NM_000212.2:c.197T>G

Uncertain Significance

BS1

BP4 PP3 BS2

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_000212.3(ITGB3):c.197T>G (p.Leu66Arg) missense variant was observed by Illumina as part of a predisposition screen in an ostensibly healthy population and has been reported in the literature in a blood donor cohort (PMID: 32110192) but has not been reported in a GT patient. There is not consensus among computational evidence as to whether there is an effect on the gene or gene product. The variant occurs at an allele frequency greater than expected for the disorder with a MAF of 0.00222 (286/129072 alleles) in the gnomAD Non-Finnish European population. In summary there is insufficient evidence resulting in a classification of Uncertain Significance. GT-specific criteria applied: BS1.

BS1

The overall allele frequency in gnomAD is 0.001765 with a MAF of 0.00222 (286/129072 alleles) in the Non-Finnish European population. This is above the threshold of >0.00158 but below the BA1 threshold of 0.0024.

BP4

The REVEL score of 0.63 falls between the >0.7 PP4 threshold and the <0.25 BP4 threshold. No effect is predicted on splicing consensus sites by MaxEntScan or HSF however HSF does predict significant alteration of ESE / ESS motifs ratio.

PP3

BS2

The variant was identified in the sample cohort of blood and platelet donors in PMID: 32110192, however full genotypes were not provided and no clinical information was available to confirm that individuals are not affected with GT.

Curation History

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