rs2738572

Positions:

• chr16-78624335-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016373.4(WWOX):​c.1056+191583A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 151,878 control chromosomes in the GnomAD database, including 41,459 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.74 (41459 hom., cov: 30)
• Consequence: WWOX NM_016373.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.805

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WWOX	NM_016373.4	c.1056+191583A>C		intron_variant		ENST00000566780.6	NP_057457.1
WWOX	NM_001291997.2	c.717+191583A>C		intron_variant			NP_001278926.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WWOX	ENST00000566780.6	c.1056+191583A>C		intron_variant		1	NM_016373.4	ENSP00000457230.1

Frequencies

GnomAD3 genomes AF: 0.737 AC: 111833 AN: 151764 Hom.: 41419 Cov.: 30

Gnomad AFR AF: 0.794

Gnomad AMI AF: 0.650

Gnomad AMR AF: 0.730

Gnomad ASJ AF: 0.762

Gnomad EAS AF: 0.701

Gnomad SAS AF: 0.660

Gnomad FIN AF: 0.627

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.729

Gnomad OTH AF: 0.732

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.737 AC: 111919 AN: 151878 Hom.: 41459 Cov.: 30 AF XY: 0.731 AC XY: 54245 AN XY: 74174

Gnomad4 AFR AF: 0.795

Gnomad4 AMR AF: 0.729

Gnomad4 ASJ AF: 0.762

Gnomad4 EAS AF: 0.701

Gnomad4 SAS AF: 0.660

Gnomad4 FIN AF: 0.627

Gnomad4 NFE AF: 0.729

Gnomad4 OTH AF: 0.728

Alfa AF: 0.730 Hom.: 8195

Bravo AF: 0.747

Asia WGS AF: 0.651 AC: 2266 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	7.7
DANN	Benign	0.48

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

Other links and lift over

dbSNP: rs2738572; hg19: chr16-78658232;