Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV001803438 | SCV002047590 | likely pathogenic | Glanzmann thrombasthenia | 2021-09-03 | reviewed by expert panel | curation | The NM_000419.5(ITGA2B):c.659A>G (p.Tyr220Cys) has been identified in at least 2 probands, including GT35 of PMID: 29675921 meeting the criteria for PP4_strong criteria. Patient GT35 of PMID: 29675921 is compound heterozygous for Tyr220Cys and c.625-1G>A (classified Pathogenic by the PD-EP) and Patient 436 of the GT database is compound heterozygous for Tyr220Cys and Ala271Gly (classified VUS by the PD-EP) (PM3_supporting). The highest population minor allele frequency in gnomAD v2.1.1 is 0.00003266 (1/30614alleles) in the South Asian population, which is lower than the ClinGen PD VCEP threshold (<0.0001) for PM2_Supporting, meeting this criterion (PM2_Supporting). In summary, this variant meets the criteria to be classified as Likely Pathogenic for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: PM2_supporting, PM3_supporting, PP4_strong. (VCEP specifications version 2; date of approval 09/02/2021) |