rs6499255

Positions:

• chr16-69796425-A-G
• chr16-69796425-A-T

Variant summary

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

The NM_001270454.2(WWP2):​c.71-2257A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 152,138 control chromosomes in the GnomAD database, including 10,789 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 0.34 (10789 hom., cov: 32)
• Consequence: WWP2 NM_001270454.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WWP2	NM_001270454.2	c.71-2257A>G		intron_variant		ENST00000359154.7	NP_001257383.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WWP2	ENST00000359154.7	c.71-2257A>G		intron_variant		1	NM_001270454.2	ENSP00000352069	P1

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51031 AN: 152020 Hom.: 10763 Cov.: 32

Gnomad AFR AF: 0.588

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.324

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

GnomAD4 genome AF: 0.336 AC: 51117 AN: 152138 Hom.: 10789 Cov.: 32 AF XY: 0.339 AC XY: 25244 AN XY: 74400

Gnomad4 AFR AF: 0.588

Gnomad4 AMR AF: 0.379

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.409

Gnomad4 SAS AF: 0.344

Gnomad4 FIN AF: 0.190

Gnomad4 NFE AF: 0.200

Gnomad4 OTH AF: 0.326

Alfa AF: 0.237 Hom.: 2412

Bravo AF: 0.360

Asia WGS AF: 0.362 AC: 1258 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	1.7
DANN	Benign	0.091

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: rs6499255; hg19: chr16-69830328;