Submissions for variant NM_006420.3(ARFGEF2):c.656dup (p.Val220fs)

dbSNP: rs730882200

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000484140	SCV000565938	pathogenic	not provided	2015-03-10	criteria provided, single submitter	clinical testing	The c.656dupC variant in the ARFGEF2 gene has not been reported previously as a pathogenic variant nor as a benign polymorphism, to our knowledge. The c.656dupC duplication causes a frameshiftstarting with codon Valine 220, changes this amino acid to a Cysteine residue and creates a premature Stopcodon at position 35 of the new reading frame, denoted p.Val220CysfsX35. This variant is predicted tocause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay.The c.656dupC variant was not observed in approximately 6,500 individuals of European and AfricanAmerican ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant inthese populations. We interpret c.656dupC as a pathogenic variant.
Department Of Translational Genomics (developmental Genetics Section), King Faisal Specialist Hospital & Research Centre	RCV000162104	SCV000196389	likely pathogenic	Global developmental delay; Seizure; Hydrocephalus	2014-12-01	no assertion criteria provided	research