Submissions for variant NM_001029896.2(WDR45):c.397C>T (p.Arg133Ter)

dbSNP: rs797046101

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000477948	SCV000249437	likely pathogenic	Neurodegeneration with brain iron accumulation 5	2015-07-07	criteria provided, single submitter	clinical testing
GeneDx	RCV000413483	SCV000491043	pathogenic	not provided	2023-04-20	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 23176820, 29981852, 25744623, 23687123, 26609730, 30369941, 25326635, 29445477, 27030146, 33084218, 33843443, 34077496)
Baylor Genetics	RCV000679876	SCV000807258	pathogenic	X-linked cerebral-cerebellar-coloboma syndrome syndrome	2017-09-01	criteria provided, single submitter	clinical testing	This variant was previously reported as pathogenic and was found once in our laboratory de novo in a 3-year-old female with infantile spasms, global developmental delay, and normal brain MRI.
Génétique des Maladies du Développement, Hospices Civils de Lyon	RCV000477948	SCV001164217	pathogenic	Neurodegeneration with brain iron accumulation 5	2018-03-06	criteria provided, single submitter	clinical testing
Invitae	RCV000477948	SCV001234057	pathogenic	Neurodegeneration with brain iron accumulation 5	2023-04-26	criteria provided, single submitter	clinical testing	This premature translational stop signal has been observed in individual(s) with neurodegeneration with brain iron accumulation (NBIA), epileptic spasms and developmental delay, and West syndrome (PMID: 23176820, 25744623, 26609730, 27030146). In at least one individual the variant was observed to be de novo. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 212592). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg134*) in the WDR45 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in WDR45 are known to be pathogenic (PMID: 23176820, 24368176, 24621584, 25744623, 26790960, 27030146, 27652284, 28554332).
CeGaT Center for Human Genetics Tuebingen	RCV000413483	SCV001247584	pathogenic	not provided	2019-10-01	criteria provided, single submitter	clinical testing
Consultorio y Laboratorio de Neurogenética, Hospital JM Ramos Mejia	RCV000477948	SCV001424331	pathogenic	Neurodegeneration with brain iron accumulation 5		criteria provided, single submitter	clinical testing
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center	RCV000477948	SCV002061746	pathogenic	Neurodegeneration with brain iron accumulation 5	2021-12-02	criteria provided, single submitter	clinical testing	PVS1, PS2, PS4, PM2
Laboratory of Human Genetics, Universidade de São Paulo	RCV000477948	SCV002506518	pathogenic	Neurodegeneration with brain iron accumulation 5	2022-03-16	criteria provided, single submitter	research	This variant meets our criteria to be classified as pathogenic based upon segregation studies, absence from controls, and in-silico evaluation of pathogenicity. This variant was disclosed in a girl presenting with intellectual disability and X-chromosome inactivation skewing.
Division of Human Genetics, Children's Hospital of Philadelphia	RCV000477948	SCV000536742	pathogenic	Neurodegeneration with brain iron accumulation 5	2016-02-09	no assertion criteria provided	research