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]

Link to SEPIO compliant JSON-LD document

Variant: NM_000212.3(ITGB3):c.285C>T (p.Leu95=)

CA8622908

696251 (ClinVar)

Gene: ITGB3

Condition: Glanzmann's thrombasthenia

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 1c295f1d-5639-44aa-b90f-86dd51a00fee

HGVS expressions

NM_000212.3:c.285C>T

NM_000212.3(ITGB3):c.285C>T (p.Leu95=)

ENST00000559488.7:c.285C>T

ENST00000559488.5:c.285C>T

ENST00000560629.1:n.250C>T

ENST00000571680.1:c.285C>T

NM_000212.2:c.285C>T

NC_000017.11:g.47283473C>T

CM000679.2:g.47283473C>T

NC_000017.10:g.45360839C>T

CM000679.1:g.45360839C>T

NC_000017.9:g.42715838C>T

NG_008332.2:g.34632C>T

Likely Benign

BP4 BP7

PP4 PM2 BS2 BS1

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.285C>T (p.Leu95=) synonymous 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. It is not predicted to have an impact on splicing and occurs at an intermediate allele frequency of 0.0004338 (56/129078 alleles) in the gnomAD non-Finnish European population. In summary, this variant meets criteria to be classified as Likely Benign for GT. GT-specific criteria applied: BS1, BP4, and BP7.

BP4

The synonymous variant is not predicted to impact the splice consensus sequence, according to MaxEntScan or SpliceAI. CADD RawScore 1.028907 PHRED 11.98

BP7

The synonymous variant is not predicted to impact the splice consensus sequence, according to MaxEntScan or SpliceAI. The nucleotide is not highly conserved (phyloP score 0.536543).

PP4

Seen once in an internal lab cohort in a 12-year-old female with a phenotype not specific to GT. The individual had autism and mild macrothrombocytopenia, epistaxis, bruising. Platelet counts 112,000-132,000/uL and MPV 10.9 fL -11.3fL (reference 7.4-10.4). No other variants in ACTN1, ANKRD26, CYCS, ETV6, FLI1, GFI1B, GP1BA, GP1BB, GP9, ITGA2B, ITGB3, MYH9, RUNX1 and TUBB1. This variant was not suspected to be responsible for disease.

PM2

This variant occurs at an intermediate allele frequency, with an overall allele frequency in gnomAD of 0.0003148 and a MAF of 0.0004338 (56/129078 alleles) in the non-Finnish European population. This is below the BS1 threshold of >0.00158 but above the PM2 threshold of <0.0001.

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.

BS1

Approved on: 2021-05-07

Published on: 2021-08-19

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