Submissions for variant NM_000130.5(F5):c.5403dup (p.Ser1802fs)

dbSNP: rs757917115

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000627559	SCV000748559	likely pathogenic	not provided	2018-03-28	criteria provided, single submitter	clinical testing	The c.5403dupA variant in the F5 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.5403dupA variant causes a frameshift starting with codon Serine 1802, changes this amino acid to an Isoleucine residue, and creates a premature Stop codon at position 3 of the new reading frame, denoted p.Ser1802IlefsX3. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.5403dupA variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). We interpret c.5403dupA as a likely pathogenic variant.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003762845	SCV004528581	pathogenic	Congenital factor V deficiency	2023-05-17	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 524063). This variant has not been reported in the literature in individuals affected with F5-related conditions. This variant is present in population databases (rs757917115, gnomAD 0.002%). This sequence change creates a premature translational stop signal (p.Ser1802Ilefs*3) in the F5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in F5 are known to be pathogenic (PMID: 30924984).