Evidence Repository
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.180C>T (p.Gly60=)

CA8622889

697901 (ClinVar)

Gene: ITGB3
Condition: Glanzmann thrombasthenia
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: 18621042-73cc-4e74-b3cb-b35c400f1ece

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

Met criteria codes 3
BS1 BP4 BP7
Not Met criteria codes 6
BA1 BS2 BP3 BP2 BP1 BP5

Evidence Links 0

Expert Panel

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.
Met criteria codes
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).
Not Met criteria codes
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS2
Two individuals were identified with the variant (PMID: 32110192) in the sample cohort of blood and platelet donors, however full genotypes were not provided and no clinical information was available to confirm that individuals are not affected with GT.
BP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Approved on: 2024-01-04
Published on: 2024-01-05
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.
¤ Powered by BCM's Genboree.