rs2738577

Positions:

• chr16-78627477-G-A
• chr16-78627477-G-C
• chr16-78627477-G-T

Variant summary

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

The NM_016373.4(WWOX):​c.1056+194725G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.588 in 152,078 control chromosomes in the GnomAD database, including 26,630 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 0.59 (26630 hom., cov: 33)
• Consequence: WWOX NM_016373.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WWOX	NM_016373.4	c.1056+194725G>A		intron_variant		ENST00000566780.6	NP_057457.1
WWOX	NM_001291997.2	c.717+194725G>A		intron_variant			NP_001278926.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WWOX	ENST00000566780.6	c.1056+194725G>A		intron_variant		1	NM_016373.4	ENSP00000457230	P1

Frequencies

GnomAD3 genomes AF: 0.588 AC: 89377 AN: 151960 Hom.: 26609 Cov.: 33

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.598

Gnomad AMR AF: 0.651

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.686

Gnomad SAS AF: 0.577

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.623

Gnomad OTH AF: 0.595

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

GnomAD4 genome AF: 0.588 AC: 89435 AN: 152078 Hom.: 26630 Cov.: 33 AF XY: 0.587 AC XY: 43628 AN XY: 74324

Gnomad4 AFR AF: 0.497

Gnomad4 AMR AF: 0.651

Gnomad4 ASJ AF: 0.635

Gnomad4 EAS AF: 0.686

Gnomad4 SAS AF: 0.576

Gnomad4 FIN AF: 0.568

Gnomad4 NFE AF: 0.623

Gnomad4 OTH AF: 0.592

Alfa AF: 0.540 Hom.: 3111

Bravo AF: 0.591

Asia WGS AF: 0.570 AC: 1982 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0010
DANN	Benign	0.18

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: rs2738577; hg19: chr16-78661374;