Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute for Clinical Chemistry and Laboratory Medicine, |
RCV002467472 | SCV002762673 | pathogenic | Inherited prekallikrein deficiency | 2022-12-12 | criteria provided, single submitter | clinical testing | We identified the variant NM_000892.4(KLKB1):c.1196G>A p.(Trp399*) in compound heterozygosity with the variant c.1643G>A in an individual with prekallikrein (PK) deficiency (1% PK activity; 6-10% PK antigen; prolonged aPTT) (Barco et al PMID: 32202057). The daughter of this index case is an asymptomatic heterozygous carrier of the latter variant. The case was originally described by Wuillemin et al as "PK Zürich" (PMID: 8259543). c.1196G>A is predicted to result in a premature stop codon in exon 11 of 15. Prediction tools coherently predict pathogenicity and there are other stop-gain variants in exon 11 known to cause PK deficiency (PMID: 32202057 and 30430790). The MAF of this variant is <0.1%. Based on this, we classified this variant as pathogenic. |