Submissions for variant NM_025132.4(WDR19):c.142dup (p.Arg48fs)

dbSNP: rs1577823005

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001008288	SCV001168055	likely pathogenic	not provided	2018-08-30	criteria provided, single submitter	clinical testing	The c.142dupA variant in the WDR19 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant causes a frameshift starting with codon Arginine 48, changes this amino acid to a Lysine residue, and creates a premature Stop codon at position 3 of the new reading frame, denoted p.Arg48LysfsX3. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.142dupA variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.142dupA as a likely pathogenic variant.
Invitae	RCV003769411	SCV004590503	pathogenic	Asphyxiating thoracic dystrophy 5; Senior-Loken syndrome 8	2022-12-30	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: 817180). This variant has not been reported in the literature in individuals affected with WDR19-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg48Lysfs*3) in the WDR19 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in WDR19 are known to be pathogenic (PMID: 22019273, 23559409, 23683095, 26275793, 27241786, 29068549).