rs1466863

Positions:

• chr16-69870235-T-A
• chr16-69870235-T-C
• chr16-69870235-T-G

Variant summary

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

The NM_001270454.2(WWP2):​c.576-1569T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 151,646 control chromosomes in the GnomAD database, including 21,535 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 0.53 (21535 hom., cov: 30)
• Consequence: WWP2 NM_001270454.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0400

Genes affected

WWP2 (HGNC:16804): (WW domain containing E3 ubiquitin protein ligase 2) This gene encodes a member of the Nedd4 family of E3 ligases, which play an important role in protein ubiquitination. The encoded protein contains four WW domains and may play a role in multiple processes including chondrogenesis and the regulation of oncogenic signaling pathways via interactions with Smad proteins and the tumor suppressor PTEN. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 10. [provided by RefSeq, Jul 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WWP2	NM_001270454.2	c.576-1569T>A		intron_variant		ENST00000359154.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WWP2	ENST00000359154.7	c.576-1569T>A		intron_variant		1	NM_001270454.2	P1

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79592 AN: 151530 Hom.: 21511 Cov.: 30

Gnomad AFR AF: 0.525

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.904

Gnomad SAS AF: 0.643

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.532

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

GnomAD4 genome AF: 0.525 AC: 79664 AN: 151646 Hom.: 21535 Cov.: 30 AF XY: 0.529 AC XY: 39194 AN XY: 74060

Gnomad4 AFR AF: 0.525

Gnomad4 AMR AF: 0.580

Gnomad4 ASJ AF: 0.455

Gnomad4 EAS AF: 0.903

Gnomad4 SAS AF: 0.644

Gnomad4 FIN AF: 0.484

Gnomad4 NFE AF: 0.486

Gnomad4 OTH AF: 0.531

Alfa AF: 0.503 Hom.: 2408

Bravo AF: 0.535

Asia WGS AF: 0.707 AC: 2455 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	1.0
DANN	Benign	0.85

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: rs1466863; hg19: chr16-69904138;