ClinVar Miner

Submissions for variant NM_000133.4(F9):c.720G>A (p.Trp240Ter)

dbSNP: rs1603265830
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Coagulation Factor Deficiency Variant Curation Expert Panel, Clingen RCV003509643 SCV004363685 pathogenic Hereditary factor IX deficiency disease 2024-02-09 reviewed by expert panel curation The NM_000133.4(F9):c.720G>A variant predicts a nonsense change, Trp240Ter, in exon 6 of the F9 gene; NMD is predicted, meeting PVS1 criteria. The variant is absent from gnomAD v2.1.1 and v3, meeting PM2_Supporting criteria. At least 8 severe hemophilia B patients meeting the F9 phenotype criteria have been reported in the literature (PMIDs: 23093250, 18479429, 8091381, 15086324), meeting PS4_Very strong. Inhibitors to factor replacement therapies have been reported (EAHAD database). In summary, the variant meets criteria to be classified as pathogenic. ACMG/AMP criteria applied, as specified by the Coagulation Factor Deficiency VCEP for F9: PVS1, PS4_Very strong, PM2_Supporting.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001000165 SCV001156653 pathogenic not specified 2019-02-13 criteria provided, single submitter clinical testing The F9 c.720G>A; p.Trp240Ter variant, also known as 20562G>A; Trp194Stop, is published in the medical literature in individuals with severe hemophilia B (Belvini 2005, Jenkins 2008). The variant is absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Considering available information, this variant is classified as pathogenic. References: Belvini D et al. Molecular genotyping of the Italian cohort of patients with hemophilia B. Haematologica. 2005 May;90(5):635-42. Jenkins PV et al. Mutation analysis of haemophilia B in the Irish population: increased prevalence caused by founder effect. Haemophilia. 2008 Jul;14(4):717-22.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.