Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
ARUP Laboratories, |
RCV001802300 | SCV002050166 | likely pathogenic | Hereditary factor VIII deficiency disease | 2021-11-12 | criteria provided, single submitter | clinical testing | The F8 c.665A>C; p.Asp222Ala variant (rs137852396), also known as Asp203Ala, is reported in the literature in individuals affected with hemophilia A (see link to FVIII database, Johnsen 2017). This variant is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. The aspartate at codon 222 is highly conserved, and computational analyses predict that this variant is deleterious (REVEL: 0.883). Additionally, other variants at this codon (c.665A>T; p.Asp222Val, c.665A>G; p.Asp222Gly) have been reported in individuals with hemophilia A (see link to FVIII database and references therein, Bogdanova 2007, Johnsen 2017). Based on available information, this variant is considered to be likely pathogenic. References: Link to FVIII database: https://f8-db.eahad.org/index.php Bogdanova N et al. Spectrum of molecular defects and mutation detection rate in patients with mild and moderate hemophilia A. Hum Mutat. 2007 Jan;28(1):54-60. PMID: 16972227. Johnsen JM et al. Novel approach to genetic analysis and results in 3000 hemophilia patients enrolled in the My Life, Our Future initiative. Blood Adv. 2017 May 18;1(13):824-834. PMID: 29296726. |