Submissions for variant NM_000132.4(F8):c.3144G>A (p.Trp1048Ter)

dbSNP: rs1060499784

Total submissions: 1

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.