16-69917388-A-G

Position:

• chr16-69917388-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.1005-321A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 152,132 control chromosomes in the GnomAD database, including 32,737 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 0.65 (32737 hom., cov: 33)
• Consequence: WWP2 NM_001270454.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WWP2	NM_001270454.2	c.1005-321A>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.1005-321A>G		intron_variant		1	NM_001270454.2	ENSP00000352069	P1

Frequencies

GnomAD3 genomes AF: 0.649 AC: 98651 AN: 152014 Hom.: 32709 Cov.: 33

Gnomad AFR AF: 0.536

Gnomad AMI AF: 0.736

Gnomad AMR AF: 0.694

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.962

Gnomad SAS AF: 0.751

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.673

Gnomad OTH AF: 0.685

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

GnomAD4 genome AF: 0.649 AC: 98737 AN: 152132 Hom.: 32737 Cov.: 33 AF XY: 0.652 AC XY: 48515 AN XY: 74366

Gnomad4 AFR AF: 0.536

Gnomad4 AMR AF: 0.694

Gnomad4 ASJ AF: 0.689

Gnomad4 EAS AF: 0.961

Gnomad4 SAS AF: 0.752

Gnomad4 FIN AF: 0.638

Gnomad4 NFE AF: 0.674

Gnomad4 OTH AF: 0.689

Alfa AF: 0.681 Hom.: 59475

Bravo AF: 0.652

Asia WGS AF: 0.830 AC: 2879 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.5
DANN	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs904809; hg19: chr16-69951291;