Variant: NM_000212.2(ITGB3):c.537C>T (p.Phe179=)

CA8622971

323864 (ClinVar)

Gene: ITGB3

Condition: Glanzmann's thrombasthenia

Inheritance Mode: Autosomal recessive inheritance

UUID: e4605fc3-1c7a-4dc7-9802-047d90e5a03c

Approved on: 2021-05-07

Published on: 2021-08-19

HGVS expressions

NM_000212.2:c.537C>T
NM_000212.2(ITGB3):c.537C>T (p.Phe179=)
NC_000017.11:g.47284618C>T
CM000679.2:g.47284618C>T
NC_000017.10:g.45361984C>T
CM000679.1:g.45361984C>T
NC_000017.9:g.42716983C>T
NG_008332.2:g.35777C>T
ENST00000559488.7:c.537C>T
ENST00000559488.5:c.537C>T
ENST00000560629.1:n.502C>T
ENST00000571680.1:c.537C>T
NM_000212.3:c.537C>T

Likely Benign

• Met criteria codes: BP4 BP7

• Not Met criteria codes: PM2 BS2 BS1

Expert Panel

Platelet Disorders VCEP

Criteria Specification Information

Evidence submitted by expert panel

Platelet Disorders VCEP

The NM_000212.2(ITGB3):c.537C>T (p.Phe179=) 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 0.0002540 (9/35438 alleles) in the gnomAD Latino population. In summary this variant meets criteria to be classified as likely benign. GT-specific criteria applied: BP4 and BP7.

Met criteria codes

• BP4: The synonymous variant is not predicted to impact the splice consensus sequence, according to MaxEntScan or SpliceAI. CADD RawScore 0.045653 PHRED 1.647
• 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 -0.488402).

Not Met criteria codes

• PM2: This variant occurs at an intermediate allele frequency, with an overall allele frequency in gnomAD of 0.0001273 and a MAF of 0.0002540 (9/35438 alleles) in the Latino 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: This variant occurs at an intermediate allele frequency, with an overall allele frequency in gnomAD of 0.0001273 and a MAF of 0.0002540 (9/35438 alleles) in the Latino population. This is below the BS1 threshold of >0.00158 but above the PM2 threshold of <0.0001.