ITGA2B p.Pro464=

The NM_000419.5(ITGA2B):c.1392A>G (p.Pro464=) has been reported in a patient (Patient 10, PMID: 31029159) with a clinical diagnosis of GT but insufficient information for a highly specific diagnosis. This variant is reported in gnomAD v4.1 in the non-Finnish European population with a MAF of 0.000001695 (2/1180034 alleles). This MAF is less than the 0.0001 MAF established by the PD VCEP to assign this code (PM2_Supporting). This variant was homozygous in the reported individual (Patient 10, PMID: 31029159) with a clinical diagnosis of GT. Since this was a homozygous occurrence and this variant was not seen in the literature elsewhere; per SVI recommendations this receives 0.5pt since this variant has a MAF of <0.0001 (PM3_Supporting). This variant was identified as heterozygous in parents and not homozygous in healthy individuals in the family. In summary, this variant meets the criteria to be classified as uncertain significance for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: PM2_supporting, PM3_Supporting (VCEP specifications version 2.1).