chr16-69796425-A-G

Variant names:

• chr16-69796425-A-G
• rs6499255
• NM_001270454.2:c.71-2257A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 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=-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 rank	MANE	Protein	UniProt
WWP2	NM_001270454.2	c.71-2257A>G		intron_variant	Intron 2 of 23	ENST00000359154.7	NP_001257383.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WWP2	ENST00000359154.7	c.71-2257A>G		intron_variant	Intron 2 of 23	1	NM_001270454.2	ENSP00000352069.2

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

African (AFR) AF: 0.588 AC: 24369 AN: 41478

American (AMR) AF: 0.379 AC: 5799 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 614 AN: 3472

East Asian (EAS) AF: 0.409 AC: 2114 AN: 5172

South Asian (SAS) AF: 0.344 AC: 1661 AN: 4826

European-Finnish (FIN) AF: 0.190 AC: 2008 AN: 10596

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.200 AC: 13595 AN: 67996

Other (OTH) AF: 0.326 AC: 689 AN: 2112

Alfa AF: 0.234 Hom.: 2597

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
PhyloP100		-2.0
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: rs6499255; hg19: chr16-69830328;