rs2859631

Positions:

• chr16-78597897-G-A
• chr16-78597897-G-C
• chr16-78597897-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_016373.4(WWOX):​c.1056+165145G>A variant causes a intron change. The variant allele was found at a frequency of 0.931 in 151,988 control chromosomes in the GnomAD database, including 66,265 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 0.93 (66265 hom., cov: 30)
• Consequence: WWOX NM_016373.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.00

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WWOX	NM_016373.4	c.1056+165145G>A		intron_variant		ENST00000566780.6	NP_057457.1
WWOX	NM_001291997.2	c.717+165145G>A		intron_variant			NP_001278926.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WWOX	ENST00000566780.6	c.1056+165145G>A		intron_variant		1	NM_016373.4	ENSP00000457230	P1

Frequencies

GnomAD3 genomes AF: 0.931 AC: 141370 AN: 151876 Hom.: 66231 Cov.: 30

Gnomad AFR AF: 0.806

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.963

Gnomad ASJ AF: 0.972

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.975

Gnomad FIN AF: 0.973

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.981

Gnomad OTH AF: 0.940

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

GnomAD4 genome AF: 0.931 AC: 141457 AN: 151988 Hom.: 66265 Cov.: 30 AF XY: 0.931 AC XY: 69110 AN XY: 74270

Gnomad4 AFR AF: 0.806

Gnomad4 AMR AF: 0.963

Gnomad4 ASJ AF: 0.972

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.976

Gnomad4 FIN AF: 0.973

Gnomad4 NFE AF: 0.981

Gnomad4 OTH AF: 0.940

Alfa AF: 0.975 Hom.: 102512

Bravo AF: 0.926

Asia WGS AF: 0.972 AC: 3379 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	19
DANN	Benign	0.82

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: rs2859631; hg19: chr16-78631794;