chr16-69870235-T-A

Variant names:

• chr16-69870235-T-A
• rs1466863
• NM_001270454.2:c.576-1569T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
WWP2	NM_001270454.2	c.576-1569T>A		intron_variant	Intron 6 of 23	ENST00000359154.7	NP_001257383.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WWP2	ENST00000359154.7	c.576-1569T>A		intron_variant	Intron 6 of 23	1	NM_001270454.2	ENSP00000352069.2

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

African (AFR) AF: 0.525 AC: 21678 AN: 41274

American (AMR) AF: 0.580 AC: 8830 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.455 AC: 1579 AN: 3472

East Asian (EAS) AF: 0.903 AC: 4662 AN: 5160

South Asian (SAS) AF: 0.644 AC: 3096 AN: 4804

European-Finnish (FIN) AF: 0.484 AC: 5060 AN: 10450

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.486 AC: 33021 AN: 67940

Other (OTH) AF: 0.531 AC: 1118 AN: 2106

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
PhyloP100		0.040
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: rs1466863; hg19: chr16-69904138;