NM_016373.4(WWOX):c.1114G>C (p.Gly372Arg) AND Autosomal recessive spinocerebellar ataxia 12

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Aug 1, 2019
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000087048.7

Allele description [Variation Report for NM_016373.4(WWOX):c.1114G>C (p.Gly372Arg)]

NM_016373.4(WWOX):c.1114G>C (p.Gly372Arg)

Genes:

MAF:MAF bZIP transcription factor [Gene - OMIM - HGNC]
WWOX:WW domain containing oxidoreductase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16q23.2

Genomic location:

Preferred name:

NM_016373.4(WWOX):c.1114G>C (p.Gly372Arg)

HGVS:

NC_000016.10:g.79211665G>C
NG_011698.1:g.1117012G>C
NM_001291997.2:c.775G>C
NM_016373.4:c.1114G>CMANE SELECT
NP_001278926.1:p.Gly259Arg
NP_057457.1:p.Gly372Arg
NC_000016.9:g.79245562G>C
NM_016373.2:c.1114G>C
Q9NZC7:p.Gly372Arg

Protein change:

G259R; GLY372ARG

Links:

UniProtKB: Q9NZC7#VAR_070993; OMIM: 605131.0003; dbSNP: rs587777127

NCBI 1000 Genomes Browser:

rs587777127

Molecular consequence:

NM_001291997.2:c.775G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_016373.4:c.1114G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Autosomal recessive spinocerebellar ataxia 12
Synonyms:: SPINOCEREBELLAR ATAXIA WITH MENTAL RETARDATION AND EPILEPSY
Identifiers:: MONDO: MONDO:0013687; MedGen: C3280452; Orphanet: 284282; OMIM: 614322

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000119862	OMIM	no assertion criteria provided	Pathogenic (Feb 1, 2014)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV001156111	Section for Clinical Neurogenetics, University of Tübingen	no assertion criteria provided	Pathogenic (Aug 1, 2019)	germline	research	PubMed (2) [See all records that cite these PMIDs] 24369382, 32214227

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000119862

OMIM

no assertion criteria provided

Pathogenic
(Feb 1, 2014)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

SCV001156111

Section for Clinical Neurogenetics, University of Tübingen

no assertion criteria provided

Pathogenic
(Aug 1, 2019)

germline

research

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	research

Citations

PubMed

The tumour suppressor gene WWOX is mutated in autosomal recessive cerebellar ataxia with epilepsy and mental retardation.

Mallaret M, Synofzik M, Lee J, Sagum CA, Mahajnah M, Sharkia R, Drouot N, Renaud M, Klein FA, Anheim M, Tranchant C, Mignot C, Mandel JL, Bedford M, Bauer P, Salih MA, Schüle R, Schöls L, Aldaz CM, Koenig M.

Brain. 2014 Feb;137(Pt 2):411-9. doi: 10.1093/brain/awt338. Epub 2013 Dec 24.

PubMed [citation]

PMID:: 24369382
PMCID:: PMC3914474

First-line exome sequencing in Palestinian and Israeli Arabs with neurological disorders is efficient and facilitates disease gene discovery.

Hengel H, Buchert R, Sturm M, Haack TB, Schelling Y, Mahajnah M, Sharkia R, Azem A, Balousha G, Ghanem Z, Falana M, Balousha O, Ayesh S, Keimer R, Deigendesch W, Zaidan J, Marzouqa H, Bauer P, Schöls L.

Eur J Hum Genet. 2020 Aug;28(8):1034-1043. doi: 10.1038/s41431-020-0609-9. Epub 2020 Mar 25. Erratum in: Eur J Hum Genet. 2022 Feb;30(2):248. doi: 10.1038/s41431-021-00909-7.

PubMed [citation]

PMID:: 32214227
PMCID:: PMC7382450

Details of each submission

From OMIM, SCV000119862.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In 2 sibs, born of consanguineous Israeli Palestinian parents, with autosomal recessive spinocerebellar ataxia-12 (SCAR12; 614322), Mallaret et al. (2014) identified a homozygous c.1114G-C transversion in exon 9 of the WWOX gene, resulting in a gly372-to-arg (G372R) substitution at a highly conserved residue in the C-terminal part of the dehydrogenase/reductase domain. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was not present in the dbSNP (build 137) or Exome Variant Server databases. Functional studies of the G372R variant were not performed.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Section for Clinical Neurogenetics, University of Tübingen, SCV001156111.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	PubMed (2)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Dec 7, 2024

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