Submissions for variant NM_014846.4(WASHC5):c.704dup (p.Tyr235Ter)

dbSNP: rs1563633906

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002233218	SCV000818807	pathogenic	Hereditary spastic paraplegia 8; Ritscher-Schinzel syndrome	2024-07-02	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Tyr235*) in the WASHC5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in WASHC5 are known to be pathogenic (PMID: 24065355). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with WASHC5-related conditions. ClinVar contains an entry for this variant (Variation ID: 570249). For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV002293471	SCV002586940	uncertain significance	not provided	2022-04-19	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene or region of a gene for which loss of function is not a well-established mechanism of disease; Has not been previously published as pathogenic or benign to our knowledge