NM_016373.4(WWOX):c.46_49del (p.Asp16fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 7, 2021
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001850176.6

Allele description [Variation Report for NM_016373.4(WWOX):c.46_49del (p.Asp16fs)]

NM_016373.4(WWOX):c.46_49del (p.Asp16fs)

Gene:

WWOX:WW domain containing oxidoreductase [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

16q23.1

Genomic location:

Preferred name:

NM_016373.4(WWOX):c.46_49del (p.Asp16fs)

HGVS:

NC_000016.10:g.78099824_78099827del
NG_011698.1:g.5171_5174del
NM_001291997.2:c.-229_-226del
NM_016373.4:c.46_49delMANE SELECT
NM_130791.5:c.46_49del
NP_057457.1:p.Asp16fs
NP_570607.1:p.Asp16fs
NC_000016.9:g.78133720_78133723del
NC_000016.9:g.78133721_78133724del
NM_016373.3:c.46_49del
NR_120435.2:n.171_174del
NR_120436.3:n.171_174del

Protein change:

D16fs

Links:

OMIM: 605131.0009; dbSNP: rs730880291

NCBI 1000 Genomes Browser:

rs730880291

Molecular consequence:

NM_001291997.2:c.-229_-226del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_016373.4:c.46_49del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_130791.5:c.46_49del - frameshift variant - [Sequence Ontology: SO:0001589]
NR_120435.2:n.171_174del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_120436.3:n.171_174del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Developmental and epileptic encephalopathy, 1 (DEE1)
Synonyms:: INFANTILE SPASM SYNDROME, X-LINKED 1; X-linked infantile spasms; West's syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010632; MedGen: C3463992; OMIM: 308350

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
SCV002245306	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 7, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 24456803, 25411445, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002245306

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 7, 2021)

germline

clinical testing

PubMed (3)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

The supposed tumor suppressor gene WWOX is mutated in an early lethal microcephaly syndrome with epilepsy, growth retardation and retinal degeneration.

Abdel-Salam G, Thoenes M, Afifi HH, Körber F, Swan D, Bolz HJ.

Orphanet J Rare Dis. 2014 Jan 23;9:12. doi: 10.1186/1750-1172-9-12.

PubMed [citation]

PMID:: 24456803
PMCID:: PMC3918143

Mignot C, Lambert L, Pasquier L, Bienvenu T, Delahaye-Duriez A, Keren B, Lefranc J, Saunier A, Allou L, Roth V, Valduga M, Moustaïne A, Auvin S, Barrey C, Chantot-Bastaraud S, Lebrun N, Moutard ML, Nougues MC, Vermersch AI, Héron B, Pipiras E, Héron D, et al.

J Med Genet. 2015 Jan;52(1):61-70. doi: 10.1136/jmedgenet-2014-102748. Epub 2014 Nov 19.

PubMed [citation]

PMID:: 25411445

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002245306.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Asp16Serfs*63) in the WWOX gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in WWOX are known to be pathogenic (PMID: 24456803, 25411445). This variant has been observed in individual(s) with infantile epileptic encephalopathy (PMID: 25411445). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 180250). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Sep 29, 2024

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Relating variation to medicine