NM_016373.4(WWOX):c.107+1_107+2delinsTA AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 25, 2023
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:: RCV003797616.2

Allele description [Variation Report for NM_016373.4(WWOX):c.107+1_107+2delinsTA]

NM_016373.4(WWOX):c.107+1_107+2delinsTA

Gene:

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

Variant type:

Indel

Cytogenetic location:

16q23.1

Genomic location:

Preferred name:

NM_016373.4(WWOX):c.107+1_107+2delinsTA

HGVS:

NC_000016.10:g.78099886_78099887delinsTA
NG_011698.1:g.5233_5234delinsTA
NG_134376.1:g.99_100delinsTA
NM_001291997.2:c.-168+1_-168+2delinsTA
NM_016373.4:c.107+1_107+2delinsTAMANE SELECT
NM_130791.5:c.107+1_107+2delinsTA
NC_000016.9:g.78133783_78133784delinsTA
NR_120435.2:n.233_234delinsTA
NR_120436.3:n.233_234delinsTA

Molecular consequence:

NR_120435.2:n.233_234delinsTA - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_120436.3:n.233_234delinsTA - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001291997.2:c.-168+1_-168+2delinsTA - splice donor variant - [Sequence Ontology: SO:0001575]
NM_016373.4:c.107+1_107+2delinsTA - splice donor variant - [Sequence Ontology: SO:0001575]
NM_130791.5:c.107+1_107+2delinsTA - splice donor variant - [Sequence Ontology: SO:0001575]

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
SCV004587113	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 25, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 16199547, 24456803, 25411445, 36537114, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004587113

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 25, 2023)

germline

clinical testing

PubMed (5)
[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

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

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

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004587113.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change affects a splice site in intron 1 of the WWOX gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in WWOX are known to be pathogenic (PMID: 24456803, 25411445). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. Disruption of this splice site has been observed in individuals with WWOX-related conditions (PMID: 36537114; Invitae). 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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