Submissions for variant NM_016373.4(WWOX):c.107+1G>A

dbSNP: rs1300924648

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Baylor Genetics	RCV000850618	SCV000992851	pathogenic	Autosomal recessive spinocerebellar ataxia 12; Developmental and epileptic encephalopathy, 28	2017-12-31	criteria provided, single submitter	clinical testing
Mendelics	RCV000989638	SCV001140167	pathogenic	Developmental and epileptic encephalopathy, 1	2019-05-28	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001858475	SCV002282490	likely pathogenic	Developmental and epileptic encephalopathy, 1; Autosomal recessive spinocerebellar ataxia 12	2022-10-12	criteria provided, single submitter	clinical testing	This variant is not present in population databases (gnomAD no frequency). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 689796). This variant has not been reported in the literature in individuals affected with WWOX-related conditions. This sequence change affects a donor 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).
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	RCV002252255	SCV002523330	likely pathogenic	See cases	2019-11-01	criteria provided, single submitter	clinical testing	ACMG classification criteria: PVS1, PM2
GeneDx	RCV003332268	SCV004039751	likely pathogenic	not provided	2023-03-24	criteria provided, single submitter	clinical testing	Reported with a second WWOX variant, phase unknown, in a patient undergoing re-analysis of clinical exome sequencing data, however detailed clinical information was not provided (Liu et al., 2019); Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 31216405)
Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	RCV003489939	SCV004232653	pathogenic	West syndrome	2023-12-15	criteria provided, single submitter	clinical testing	Zygosity: Compound heterozygous with a deletion spanning exons 1-5 in the WWOX gene.