Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV001225258 | SCV001397519 | likely pathogenic | Glanzmann thrombasthenia | 2023-06-01 | reviewed by expert panel | curation | The NM_000419.5(ITGA2B):c.480C>G variant causes a missense change, Ser160Arg, that predicted to have a damaging impact on splicing, SpliceAI predicts activation of an exonic cryptic acceptor site (score 0.76; PP3) with could cause loss of 33 amino acids. PMID: 9215749 reports that this results in the in-frame deletion of Ser160_Ser192 in exon 4 (PM4). It is reported in 3 compound heterozygous individuals (PMID: 9215749, 28232155, 32237906) including in trans with c.1545-1del (classified as pathogenic by the Platelet Disorders VCEP) from PMID: 32237906, as well as one homozygote in https://cdmd.cnki.com.cn/Article/CDMD-10661-1019864182.htm (PM3). At least two of the probands meet the criteria for PP4_moderate, including mucocutaneous bleeding and impaired aggregation with all agonists except ristocetin (PMIDs: 32237906 and 28232155). 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: PP4_moderate, PM2_supporting, PM3, PP3, PM4. (VCEP specifications version 2). |
ISTH- |
RCV002280900 | SCV002569359 | likely pathogenic | Glanzmann thrombasthenia 1 | criteria provided, single submitter | clinical testing |