NM_016373.4(WWOX):c.49G>A (p.Glu17Lys) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 21, 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:: RCV001869806.4

Allele description [Variation Report for NM_016373.4(WWOX):c.49G>A (p.Glu17Lys)]

NM_016373.4(WWOX):c.49G>A (p.Glu17Lys)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

16q23.1

Genomic location:

Preferred name:

NM_016373.4(WWOX):c.49G>A (p.Glu17Lys)

HGVS:

NC_000016.10:g.78099827G>A
NG_011698.1:g.5174G>A
NM_001291997.2:c.-226G>A
NM_016373.4:c.49G>AMANE SELECT
NM_130791.5:c.49G>A
NP_057457.1:p.Glu17Lys
NP_570607.1:p.Glu17Lys
NC_000016.9:g.78133724G>A
NR_120435.2:n.174G>A
NR_120436.3:n.174G>A

Protein change:

E17K

Links:

dbSNP: rs780345312

NCBI 1000 Genomes Browser:

rs780345312

Molecular consequence:

NM_001291997.2:c.-226G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_016373.4:c.49G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_130791.5:c.49G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_120435.2:n.174G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_120436.3:n.174G>A - 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
SCV002126887	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 21, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 30356099, 31618474, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002126887

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 21, 2023)

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 phenotypic spectrum of WWOX-related disorders: 20 additional cases of WOREE syndrome and review of the literature.

Piard J, Hawkes L, Milh M, Villard L, Borgatti R, Romaniello R, Fradin M, Capri Y, Héron D, Nougues MC, Nava C, Arsene OT, Shears D, Taylor J, Pagnamenta A, Taylor JC, Sogawa Y, Johnson D, Firth H, Vasudevan P, Jones G, Nguyen-Morel MA, et al.

Genet Med. 2019 Jun;21(6):1308-1318. doi: 10.1038/s41436-018-0339-3. Epub 2018 Oct 25. Review. Erratum in: Genet Med. 2019 Jul;21(7):1667-1671. doi: 10.1038/s41436-019-0460-y.

PubMed [citation]

PMID:: 30356099
PMCID:: PMC6752669

The Genetic Landscape of Epilepsy of Infancy with Migrating Focal Seizures.

Burgess R, Wang S, McTague A, Boysen KE, Yang X, Zeng Q, Myers KA, Rochtus A, Trivisano M, Gill D; EIMFS Consortium., Sadleir LG, Specchio N, Guerrini R, Marini C, Zhang YH, Mefford HC, Kurian MA, Poduri AH, Scheffer IE.

Ann Neurol. 2019 Dec;86(6):821-831. doi: 10.1002/ana.25619. Erratum in: Ann Neurol. 2020 Apr;87(4):658. doi: 10.1002/ana.25703.

PubMed [citation]

PMID:: 31618474
PMCID:: PMC7423163

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002126887.3

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

Description

This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 17 of the WWOX protein (p.Glu17Lys). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 1338792). This missense change has been observed in individuals with developmental and epileptic encephalopathy (PMID: 30356099, 31618474). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database.

#	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: Nov 3, 2024

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