ClinVar Miner

Submissions for variant NM_000132.3(F8):c.3144G>A (p.Trp1048Ter) (rs1060499784)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Knight Diagnostic Laboratories,Oregon Health and Sciences University RCV000454124 SCV000538026 likely pathogenic Hereditary factor VIII deficiency disease 2016-01-27 criteria provided, single submitter clinical testing The c.3144G>A (p.Trp1048*) nonsense variant in the F8 gene has not been previously reported; however, pathogenic variants occurring in the same codon and leading to the same nonsense change have previously been reported in individuals affected with severe Hemophilia A (Leuer et al., 2001; Hill et al., 2005). This c.3144G>A variant is predicted to cause a protein termination in exon 14 (out of a total of 26 exons in the coding sequence). Nonsense variants have been described in the F8 gene in several affected individuals (including nonsense variants downstream of this p.Trp1048* variant) and are, therefore, a common mechanism of disease. This c.3144G>A has not been reported in the population databases (Exome Sequencing Project [ESP], 1000 Genomes, and ExAC). In silico algorithms predict this variant has a deleterious effect (GERP = 4.42; CADD = 40). Therefore, this collective evidence supports the classification of the c.3144G>A (p.Trp1048*) as an X-linked recessive Likely Pathogenic variant for Hemophilia A.

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