Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
ISTH- |
RCV002223108 | SCV002500864 | pathogenic | Hereditary factor VIII deficiency disease | criteria provided, single submitter | clinical testing | ||
Genetics and Molecular Pathology, |
RCV002223108 | SCV004175478 | uncertain significance | Hereditary factor VIII deficiency disease | 2023-04-14 | criteria provided, single submitter | clinical testing | The F8 c.2150G>T variant is classified as VUS (PS4_Supp, PM2, PM5-supp, PP3) The F8 c.2150G>T variant is a single nucleotide change in exon 14/26 of the F8 gene, which is predicted to change the amino acid arginine at position 717 in the protein to leucine. The variant has been reported in 2 index cases with a clinical presentation of mild haemophilia, one of which demonstrated one-stage/two-stage assay discrepancy (PMID: 8759905, 16173970 (PS4_Supporting). This variant is absent from population databases (PM2). This variant is a missense change at an amino acid residue where a different missense change, c.2149C>T(p.Arg717Trp) and c.2150G>A (p.Arg717Gln), has been seen before (PM5-supp). in silico pathogenicity predicts suggest that the variant has a deleterious effect on the protein (REVEL score 0.874) and it is located in a functional domain (PMID: 19473423, 18299331) PP3. The variant has been reported in the HGMD database: CM960551 and has been reported as Pathogenic by one other diagnostic laboratory (ClinVar Variation ID: 1677257). It has not been reported in dbSNP. |