16-69816248-G-C

Variant names:

• chr16-69816248-G-C
• rs4608327
• NM_001270454.2:c.340+16953G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001270454.2(WWP2):​c.340+16953G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.781 in 151,540 control chromosomes in the GnomAD database, including 46,559 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 0.78 (46559 hom., cov: 29)
• Consequence: WWP2 NM_001270454.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32
• Publications: 4 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.844 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001270454.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WWP2	NM_001270454.2	MANE Select	c.340+16953G>C		intron	N/A	NP_001257383.1
	WWP2	NM_007014.5		c.340+16953G>C		intron	N/A	NP_008945.2
	WWP2	NM_001270455.2		c.340+16953G>C		intron	N/A	NP_001257384.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WWP2	ENST00000359154.7	TSL:1 MANE Select	c.340+16953G>C		intron	N/A	ENSP00000352069.2
	WWP2	ENST00000569174.5	TSL:5	c.340+16953G>C		intron	N/A	ENSP00000455311.1
	WWP2	ENST00000544162.5	TSL:2	n.212+16953G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.781 AC: 118317 AN: 151422 Hom.: 46530 Cov.: 29

Gnomad AFR AF: 0.728

Gnomad AMI AF: 0.748

Gnomad AMR AF: 0.856

Gnomad ASJ AF: 0.749

Gnomad EAS AF: 0.611

Gnomad SAS AF: 0.801

Gnomad FIN AF: 0.810

Gnomad MID AF: 0.739

Gnomad NFE AF: 0.806

Gnomad OTH AF: 0.790

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

GnomAD4 genome AF: 0.781 AC: 118392 AN: 151540 Hom.: 46559 Cov.: 29 AF XY: 0.782 AC XY: 57907 AN XY: 74042

African (AFR) AF: 0.728 AC: 30053 AN: 41282

American (AMR) AF: 0.856 AC: 13020 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.749 AC: 2599 AN: 3470

East Asian (EAS) AF: 0.611 AC: 3145 AN: 5150

South Asian (SAS) AF: 0.802 AC: 3850 AN: 4802

European-Finnish (FIN) AF: 0.810 AC: 8426 AN: 10408

Middle Eastern (MID) AF: 0.733 AC: 214 AN: 292

European-Non Finnish (NFE) AF: 0.806 AC: 54742 AN: 67912

Other (OTH) AF: 0.789 AC: 1662 AN: 2106

Alfa AF: 0.760 Hom.: 2392

Bravo AF: 0.780

Asia WGS AF: 0.739 AC: 2569 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.35
DANN	Benign	0.31
PhyloP100		-1.3
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: rs4608327; hg19: chr16-69850151;