16-78424853-G-A

Position:

chr16-78424853-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000566780.6(WWOX):c.606-17G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,613,034 control chromosomes in the GnomAD database, including 20,608 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 8191 hom., cov: 32)

Exomes 𝑓: 0.094 ( 12417 hom. )

Consequence

WWOX
ENST00000566780.6 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.510

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 16-78424853-G-A is Benign according to our data. Variant chr16-78424853-G-A is described in ClinVar as [Benign]. Clinvar id is 260742.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-78424853-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WWOX	NM_016373.4 linkuse as main transcript	c.606-17G>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000566780.6	NP_057457.1
WWOX	NM_001291997.2 linkuse as main transcript	c.267-17G>A		splice_polypyrimidine_tract_variant, intron_variant			NP_001278926.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WWOX	ENST00000566780.6 linkuse as main transcript	c.606-17G>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_016373.4	ENSP00000457230	P1	Q9NZC7-1

Frequencies

GnomAD3 genomes

AF:

0.233

AC:

35326

AN:

151846

Hom.:

8161

Cov.:

show subpopulations

Gnomad AFR

AF:

0.600

Gnomad AMI

AF:

0.0428

Gnomad AMR

AF:

0.143

Gnomad ASJ

AF:

0.129

Gnomad EAS

AF:

0.187

Gnomad SAS

AF:

0.151

Gnomad FIN

AF:

0.0906

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.0706

Gnomad OTH

AF:

0.190

GnomAD3 exomes

AF:

0.133

AC:

33197

AN:

248764

Hom.:

4339

AF XY:

0.126

AC XY:

17036

AN XY:

135152

show subpopulations

Gnomad AFR exome

AF:

0.614

Gnomad AMR exome

AF:

0.117

Gnomad ASJ exome

AF:

0.131

Gnomad EAS exome

AF:

0.186

Gnomad SAS exome

AF:

0.148

Gnomad FIN exome

AF:

0.0905

Gnomad NFE exome

AF:

0.0721

Gnomad OTH exome

AF:

0.116

GnomAD4 exome

AF:

0.0939

AC:

137157

AN:

1461070

Hom.:

12417

Cov.:

AF XY:

0.0937

AC XY:

68082

AN XY:

726920

show subpopulations

Gnomad4 AFR exome

AF:

0.625

Gnomad4 AMR exome

AF:

0.120

Gnomad4 ASJ exome

AF:

0.133

Gnomad4 EAS exome

AF:

0.169

Gnomad4 SAS exome

AF:

0.146

Gnomad4 FIN exome

AF:

0.0926

Gnomad4 NFE exome

AF:

0.0674

Gnomad4 OTH exome

AF:

0.125

GnomAD4 genome

AF:

0.233

AC:

35408

AN:

151964

Hom.:

8191

Cov.:

AF XY:

0.231

AC XY:

17144

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.601

Gnomad4 AMR

AF:

0.143

Gnomad4 ASJ

AF:

0.129

Gnomad4 EAS

AF:

0.187

Gnomad4 SAS

AF:

0.150

Gnomad4 FIN

AF:

0.0906

Gnomad4 NFE

AF:

0.0706

Gnomad4 OTH

AF:

0.188

Alfa

AF:

0.0961

Hom.:

1543

Bravo

AF:

0.251

Asia WGS

AF:

0.205

AC:

717

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jul 15, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 23% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 21. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 12, 2016	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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Developmental and epileptic encephalopathy, 28

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Autosomal recessive spinocerebellar ataxia 12

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.88

DANN

Benign

0.45

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over