rs12934985

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016373.4(WWOX):c.409+16A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 1,613,652 control chromosomes in the GnomAD database, including 66,698 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 4675 hom., cov: 33)

Exomes 𝑓: 0.29 ( 62023 hom. )

Consequence

WWOX
NM_016373.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.0300

Publications

6 publications found

Variant links:

Genes affected

WWOX (HGNC:12799): (WW domain containing oxidoreductase) This gene encodes a member of the short-chain dehydrogenases/reductases (SDR) protein family. This gene spans the FRA16D common chromosomal fragile site and appears to function as a tumor suppressor gene. Expression of the encoded protein is able to induce apoptosis, while defects in this gene are associated with multiple types of cancer. Disruption of this gene is also associated with autosomal recessive spinocerebellar ataxia 12. Disruption of a similar gene in mouse results in impaired steroidogenesis, additionally suggesting a metabolic function for the protein. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

WWOX Gene-Disease associations (from GenCC):

genetic developmental and epileptic encephalopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
autosomal recessive spinocerebellar ataxia 12
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
developmental and epileptic encephalopathy, 28
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
46,XY partial gonadal dysgenesis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
undetermined early-onset epileptic encephalopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

WWOX links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 16-78115170-A-C is Benign according to our data. Variant chr16-78115170-A-C is described in ClinVar as [Benign]. Clinvar id is 260738.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
WWOX	NM_016373.4 link	c.409+16A>C	intron_variant	Intron 4 of 8	ENST00000566780.6	NP_057457.1	Q9NZC7-1A0A411HBC7
WWOX	NM_001291997.2 link	c.70+16A>C	intron_variant	Intron 3 of 7		NP_001278926.1	Q9NZC7
WWOX	NM_130791.5 link	c.409+16A>C	intron_variant	Intron 4 of 5		NP_570607.1	Q9NZC7-3
WWOX	NR_120436.3 link	n.648+16A>C	intron_variant	Intron 4 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WWOX	ENST00000566780.6 link	c.409+16A>C		intron_variant	Intron 4 of 8	1	NM_016373.4	ENSP00000457230.1		Q9NZC7-1

Frequencies

GnomAD3 genomes

AF:

0.225

AC:

34230

AN:

152086

Hom.:

4672

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0567

Gnomad AMI

AF:

0.319

Gnomad AMR

AF:

0.219

Gnomad ASJ

AF:

0.292

Gnomad EAS

AF:

0.235

Gnomad SAS

AF:

0.234

Gnomad FIN

AF:

0.344

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.305

Gnomad OTH

AF:

0.211

GnomAD2 exomes

AF:

0.262

AC:

65189

AN:

248674

AF XY:

0.266

show subpopulations

Gnomad AFR exome

AF:

0.0530

Gnomad AMR exome

AF:

0.226

Gnomad ASJ exome

AF:

0.287

Gnomad EAS exome

AF:

0.255

Gnomad FIN exome

AF:

0.334

Gnomad NFE exome

AF:

0.295

Gnomad OTH exome

AF:

0.265

GnomAD4 exome

AF:

0.286

AC:

418320

AN:

1461448

Hom.:

62023

Cov.:

AF XY:

0.285

AC XY:

207177

AN XY:

727026

show subpopulations

African (AFR)

AF:

0.0471

AC:

1578

AN:

33480

American (AMR)

AF:

0.224

AC:

10029

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.282

AC:

7359

AN:

26128

East Asian (EAS)

AF:

0.221

AC:

8790

AN:

39694

South Asian (SAS)

AF:

0.238

AC:

20502

AN:

86242

European-Finnish (FIN)

AF:

0.330

AC:

17636

AN:

53414

Middle Eastern (MID)

AF:

0.185

AC:

1066

AN:

5768

European-Non Finnish (NFE)

AF:

0.302

AC:

335173

AN:

1111622

Other (OTH)

AF:

0.268

AC:

16187

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

15067

30134

45202

60269

75336

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.225

AC:

34225

AN:

152204

Hom.:

4675

Cov.:

AF XY:

0.226

AC XY:

16808

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.0566

AC:

2351

AN:

41560

American (AMR)

AF:

0.219

AC:

3351

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.292

AC:

1013

AN:

3468

East Asian (EAS)

AF:

0.235

AC:

1213

AN:

5164

South Asian (SAS)

AF:

0.234

AC:

1129

AN:

4820

European-Finnish (FIN)

AF:

0.344

AC:

3641

AN:

10582

Middle Eastern (MID)

AF:

0.187

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.305

AC:

20739

AN:

67992

Other (OTH)

AF:

0.209

AC:

442

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1311

2622

3932

5243

6554

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.224

Hom.:

1161

Bravo

AF:

0.210

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 06, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 42% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 39. Only high quality variants are reported. -

Autosomal recessive spinocerebellar ataxia 12;C3463992:Developmental and epileptic encephalopathy, 1

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Developmental and epileptic encephalopathy, 28

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Autosomal recessive spinocerebellar ataxia 12

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.13

(source)

DANN

Benign

0.64

PhyloP100

-0.030

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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rs12934985

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over