rs2550710

Variant names:

• chr16-79023247-A-C
• rs2550710
• NM_016373.4:c.1057-188361A>C

Your query was ambiguous. Multiple possible variants found:

• chr16-79023247-A-C
• chr16-79023247-A-G
• chr16-79023247-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016373.4(WWOX):​c.1057-188361A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.775 in 152,146 control chromosomes in the GnomAD database, including 46,280 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 0.77 (46280 hom., cov: 32)
• Consequence: WWOX NM_016373.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0800
• Publications: 5 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WWOX	NM_016373.4	c.1057-188361A>C		intron_variant	Intron 8 of 8	ENST00000566780.6	NP_057457.1
WWOX	NM_001291997.2	c.718-188361A>C		intron_variant	Intron 7 of 7		NP_001278926.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WWOX	ENST00000566780.6	c.1057-188361A>C		intron_variant	Intron 8 of 8	1	NM_016373.4	ENSP00000457230.1

Frequencies

GnomAD3 genomes AF: 0.775 AC: 117784 AN: 152028 Hom.: 46224 Cov.: 32

Gnomad AFR AF: 0.876

Gnomad AMI AF: 0.634

Gnomad AMR AF: 0.816

Gnomad ASJ AF: 0.708

Gnomad EAS AF: 0.947

Gnomad SAS AF: 0.692

Gnomad FIN AF: 0.675

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.718

Gnomad OTH AF: 0.777

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

GnomAD4 genome AF: 0.775 AC: 117898 AN: 152146 Hom.: 46280 Cov.: 32 AF XY: 0.772 AC XY: 57394 AN XY: 74372

African (AFR) AF: 0.876 AC: 36367 AN: 41512

American (AMR) AF: 0.817 AC: 12486 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.708 AC: 2457 AN: 3472

East Asian (EAS) AF: 0.947 AC: 4891 AN: 5166

South Asian (SAS) AF: 0.690 AC: 3324 AN: 4814

European-Finnish (FIN) AF: 0.675 AC: 7134 AN: 10576

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.718 AC: 48806 AN: 67998

Other (OTH) AF: 0.781 AC: 1650 AN: 2114

Alfa AF: 0.742 Hom.: 78579

Bravo AF: 0.795

Asia WGS AF: 0.820 AC: 2851 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.1
DANN	Benign	0.65
PhyloP100		0.080
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2550710; hg19: chr16-79057144;