16-69834440-A-G

Position:

• chr16-69834440-A-G

Variant summary

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

The NM_001270454.2(WWP2):​c.341-5686A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.854 in 152,094 control chromosomes in the GnomAD database, including 55,664 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 0.85 (55664 hom., cov: 31)
• Consequence: WWP2 NM_001270454.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.30

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.898 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WWP2	NM_001270454.2	c.341-5686A>G		intron_variant		ENST00000359154.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WWP2	ENST00000359154.7	c.341-5686A>G		intron_variant		1	NM_001270454.2	P1

Frequencies

GnomAD3 genomes AF: 0.854 AC: 129742 AN: 151978 Hom.: 55624 Cov.: 31

Gnomad AFR AF: 0.820

Gnomad AMI AF: 0.880

Gnomad AMR AF: 0.910

Gnomad ASJ AF: 0.821

Gnomad EAS AF: 0.614

Gnomad SAS AF: 0.825

Gnomad FIN AF: 0.881

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.878

Gnomad OTH AF: 0.861

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

GnomAD4 genome AF: 0.854 AC: 129835 AN: 152094 Hom.: 55664 Cov.: 31 AF XY: 0.852 AC XY: 63378 AN XY: 74348

Gnomad4 AFR AF: 0.820

Gnomad4 AMR AF: 0.911

Gnomad4 ASJ AF: 0.821

Gnomad4 EAS AF: 0.614

Gnomad4 SAS AF: 0.825

Gnomad4 FIN AF: 0.881

Gnomad4 NFE AF: 0.878

Gnomad4 OTH AF: 0.860

Alfa AF: 0.870 Hom.: 25818

Bravo AF: 0.854

Asia WGS AF: 0.763 AC: 2657 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.4
DANN	Benign	0.77

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: rs2088747; hg19: chr16-69868343;