dbSNP rs1052429: WWP2:c.*1517G>A (chr16-69941457-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.36

Publications

21 publications found

Variant links:

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]

WWP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
WWP2	NM_001270454.2	MANE Select	c.*1517G>A	3_prime_UTR	Exon 24 of 24	NP_001257383.1	O00308-1
WWP2	NM_007014.5		c.*1517G>A	3_prime_UTR	Exon 25 of 25	NP_008945.2
WWP2	NM_001270453.2		c.*1517G>A	3_prime_UTR	Exon 21 of 21	NP_001257382.1	O00308-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
WWP2	ENST00000359154.7	TSL:1 MANE Select	c.*1517G>A	3_prime_UTR	Exon 24 of 24	ENSP00000352069.2	O00308-1
WWP2	ENST00000903147.1		c.*1517G>A	3_prime_UTR	Exon 25 of 25	ENSP00000573206.1
WWP2	ENST00000903148.1		c.*1517G>A	3_prime_UTR	Exon 25 of 25	ENSP00000573207.1

Frequencies

GnomAD3 genomes

AF:

0.804

AC:

122201

AN:

152044

Hom.:

49625

Cov.:

show subpopulations

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.:

AF XY:

0.788

AC XY:

662

AN XY:

840

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.783

AC:

1203

AN:

1536

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.711

AC:

AN:

Other (OTH)

AF:

0.667

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

103

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.804

AC:

122318

AN:

152162

Hom.:

49678

Cov.:

AF XY:

0.807

AC XY:

60019

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.920

AC:

38191

AN:

41524

American (AMR)

AF:

0.783

AC:

11974

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.774

AC:

2686

AN:

3470

East Asian (EAS)

AF:

0.962

AC:

4947

AN:

5142

South Asian (SAS)

AF:

0.798

AC:

3851

AN:

4828

European-Finnish (FIN)

AF:

0.773

AC:

8193

AN:

10594

Middle Eastern (MID)

AF:

0.765

AC:

225

AN:

294

European-Non Finnish (NFE)

AF:

0.733

AC:

49845

AN:

68006

Other (OTH)

AF:

0.807

AC:

1704

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1189

2378

3568

4757

5946

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

870

1740

2610

3480

4350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.756

Hom.:

186809

Bravo

AF:

0.813

Asia WGS

AF:

0.856

AC:

2975

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.021

(source)

DANN

Benign

0.53

PhyloP100

-2.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over