rs1052429

Positions:

• chr16-69941457-G-A
• chr16-69941457-G-C
• chr16-69941457-G-T

Variant summary

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

The NM_001270454.2(WWP2):​c.*1517G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.804 in 153,760 control chromosomes in the GnomAD database, including 50,160 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 0.80 (49678 hom., cov: 32)
  • Exomes 𝑓: 0.78 (482 hom.)
• Consequence: WWP2 NM_001270454.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.36

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WWP2	NM_001270454.2	c.*1517G>A		3_prime_UTR_variant	24/24	ENST00000359154.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WWP2	ENST00000359154.7	c.*1517G>A		3_prime_UTR_variant	24/24	1	NM_001270454.2	P1
WWP2	ENST00000356003.6	c.*1517G>A		3_prime_UTR_variant	21/21	2
WWP2	ENST00000568684.1	c.*1517G>A		3_prime_UTR_variant	14/14	2

Frequencies

GnomAD3 genomes AF: 0.804 AC: 122201 AN: 152044 Hom.: 49625 Cov.: 32

Gnomad AFR AF: 0.920

Gnomad AMI AF: 0.773

Gnomad AMR AF: 0.783

Gnomad ASJ AF: 0.774

Gnomad EAS AF: 0.963

Gnomad SAS AF: 0.797

Gnomad FIN AF: 0.773

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.733

Gnomad OTH AF: 0.807

GnomAD4 exome AF: 0.781 AC: 1248 AN: 1598 Hom.: 482 Cov.: 0 AF XY: 0.788 AC XY: 662 AN XY: 840

Gnomad4 AFR exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.783

Gnomad4 NFE exome AF: 0.711

Gnomad4 OTH exome AF: 0.667

GnomAD4 genome AF: 0.804 AC: 122318 AN: 152162 Hom.: 49678 Cov.: 32 AF XY: 0.807 AC XY: 60019 AN XY: 74388

Gnomad4 AFR AF: 0.920

Gnomad4 AMR AF: 0.783

Gnomad4 ASJ AF: 0.774

Gnomad4 EAS AF: 0.962

Gnomad4 SAS AF: 0.798

Gnomad4 FIN AF: 0.773

Gnomad4 NFE AF: 0.733

Gnomad4 OTH AF: 0.807

Alfa AF: 0.751 Hom.: 86781

Bravo AF: 0.813

Asia WGS AF: 0.856 AC: 2975 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.021
DANN	Benign	0.53

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: rs1052429; hg19: chr16-69975360;