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.180C>T (p.Gly60=)

Curation Version - 2.0
Curation History
JSON LD for Version 2.0

CA8622889

697901 (ClinVar)

Gene: ITGB3

Condition: Glanzmann thrombasthenia

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 18621042-73cc-4e74-b3cb-b35c400f1ece

Approved on: 2024-01-04

Published on: 2024-01-05

HGVS expressions

NM_000212.3:c.180C>T

NM_000212.3(ITGB3):c.180C>T (p.Gly60=)

NC_000017.11:g.47283368C>T

CM000679.2:g.47283368C>T

NC_000017.10:g.45360734C>T

CM000679.1:g.45360734C>T

NC_000017.9:g.42715733C>T

NG_008332.2:g.34527C>T

ENST00000559488.7:c.180C>T

ENST00000559488.5:c.180C>T

ENST00000560629.1:c.145C>T

ENST00000571680.1:c.180C>T

NM_000212.2:c.180C>T

Likely Benign

BS1 BP4 BP7

BA1 BS2 BP3 BP2 BP1 BP5

Evidence Links 0

Expert Panel

Platelet Disorders VCEP

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.180C>T (p.Gly60=) 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 Glanzmann thrombasthenia patient. It is not predicted to have an impact on splicing (BP4) and is not highly conserved (phyloP score -0.693504; BP7). The highest population minor allele frequency in gnomAD v4.0.0 is 0.002794 (17/6084 alleles) in the Middle Eastern population, which is higher than the ClinGen PD VCEP BS1 threshold (>0.00158). In summary this variant meets criteria to be classified as likely benign. GT-specific criteria applied: BS1, BP4 and BP7.

BS1

The highest population minor allele frequency in gnomAD v4.0.0 is 0.002794 (17/6084 alleles) in the Middle Eastern population, which is higher than the ClinGen PD VCEP BA1 threshold (>0.0024), due to this being a bottle-necked population this was downgraded to BS1. The next highest minor allele frequency in gnomAD v4.0.0 is 0.0003118 (14/44896 alleles) in the East Asian population.

BP4

The intronic variant is not predicted to impact the splice consensus sequence, according to MaxEntScan or SpliceAI. CADD RawScore 0.363053 PHRED 5.013

BP7

The intronic variant is not predicted to impact the splice consensus sequence, according to MaxEntScan or SpliceAI. The nucleotide is not highly conserved (phyloP score -0.693504).

BA1