Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV001803421 | SCV002047572 | pathogenic | Glanzmann thrombasthenia | 2021-06-30 | reviewed by expert panel | curation | The NM_000419.5(ITGA2B):c.1993C>T (p.Gln665Ter) nonsense variant creates a premature stop codon in exon 20/30 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). At least one proband has been reported with this variant, GT37 of PMID: 29675921 who meets the criteria for PP4_strong. GT37 is homozygous for Gln665Ter (PM3_supporting). The highest population minor allele frequency in gnomAD 2.1.1 is 0.00005461 (1/18310alleles) in the East Asian population (PM2_Supporting). In summary, this variant meets the criteria to be classified as Pathogenic for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: PVS1, PM2_supporting, PM3_supporting, PP4_strong. (VCEP specifications version 2; date of approval xx/xx/xxxx) |