16-69798745-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001270454.2(WWP2):​c.134C>T​(p.Ala45Val) variant causes a missense change. The variant allele was found at a frequency of 0.000088 in 1,613,806 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00015 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000081 ( 0 hom. )

Consequence

WWP2
NM_001270454.2 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.16
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.10669449).
BS2
High AC in GnomAd4 at 23 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
WWP2NM_001270454.2 linkc.134C>T p.Ala45Val missense_variant Exon 3 of 24 ENST00000359154.7 NP_001257383.1 O00308-1A0A024R711

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
WWP2ENST00000359154.7 linkc.134C>T p.Ala45Val missense_variant Exon 3 of 24 1 NM_001270454.2 ENSP00000352069.2 O00308-1

Frequencies

GnomAD3 genomes
AF:
0.000151
AC:
23
AN:
151970
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000484
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000787
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000946
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.000479
GnomAD3 exomes
AF:
0.000107
AC:
27
AN:
251332
Hom.:
0
AF XY:
0.0000883
AC XY:
12
AN XY:
135824
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000347
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000123
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000814
AC:
119
AN:
1461836
Hom.:
0
Cov.:
30
AF XY:
0.0000798
AC XY:
58
AN XY:
727218
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.000291
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000899
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
AF:
0.000151
AC:
23
AN:
151970
Hom.:
0
Cov.:
31
AF XY:
0.000229
AC XY:
17
AN XY:
74210
show subpopulations
Gnomad4 AFR
AF:
0.0000484
Gnomad4 AMR
AF:
0.000787
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000946
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.000479
Alfa
AF:
0.0000831
Hom.:
0
Bravo
AF:
0.000155
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000659
AC:
8
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000119

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 11, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.134C>T (p.A45V) alteration is located in exon 4 (coding exon 2) of the WWP2 gene. This alteration results from a C to T substitution at nucleotide position 134, causing the alanine (A) at amino acid position 45 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.084
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.11
CADD
Uncertain
26
DANN
Uncertain
0.98
DEOGEN2
Benign
0.043
T;T;T;.
Eigen
Benign
0.0032
Eigen_PC
Uncertain
0.23
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.85
T;D;D;D
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.11
T;T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.95
L;.;.;L
PrimateAI
Uncertain
0.67
T
PROVEAN
Benign
-0.68
N;N;D;N
REVEL
Benign
0.13
Sift
Benign
1.0
T;T;D;T
Sift4G
Benign
0.30
T;D;T;D
Polyphen
0.059
B;.;.;.
Vest4
0.54
MVP
0.23
MPC
0.35
ClinPred
0.049
T
GERP RS
5.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.7
Varity_R
0.29
gMVP
0.40

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs140261430; hg19: chr16-69832648; API