NM_012478.4:c.487A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012478.4(WBP2):​c.487A>C​(p.Met163Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as no classifications from unflagged records (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

WBP2
NM_012478.4 missense

Scores

1
2
16

Clinical Significance

no classifications from unflagged records no classifications from unflagged records P:1

Conservation

PhyloP100: 2.50

Publications

1 publications found
Variant links:
Genes affected
WBP2 (HGNC:12738): (WW domain binding protein 2) The globular WW domain is composed of 38 to 40 semiconserved amino acids shared by proteins of diverse functions including structural, regulatory, and signaling proteins. The domain is involved in mediating protein-protein interactions through the binding of polyproline ligands. This gene encodes a WW domain binding protein that is a transcriptional coactivator of estrogen receptor alpha and progesterone receptor. Defects in this gene have been associated with hearing impairment. [provided by RefSeq, Jan 2017]
WBP2 Gene-Disease associations (from GenCC):
  • hearing loss, autosomal recessive 107
    Inheritance: AR, Unknown Classification: MODERATE, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
  • hearing loss, autosomal recessive
    Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: ClinGen, Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2271018).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
WBP2NM_012478.4 linkc.487A>C p.Met163Leu missense_variant Exon 5 of 8 ENST00000254806.8 NP_036610.2
WBP2NM_001348170.1 linkc.487A>C p.Met163Leu missense_variant Exon 6 of 9 NP_001335099.1
WBP2XM_047435712.1 linkc.421A>C p.Met141Leu missense_variant Exon 5 of 8 XP_047291668.1
WBP2NM_001330499.2 linkc.398-232A>C intron_variant Intron 4 of 6 NP_001317428.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
WBP2ENST00000254806.8 linkc.487A>C p.Met163Leu missense_variant Exon 5 of 8 1 NM_012478.4 ENSP00000254806.3 Q969T9-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Significance: no classifications from unflagged records
Submissions summary: Pathogenic:1
Revision: no classifications from unflagged records
LINK: link

Submissions by phenotype

Hearing loss, autosomal recessive 107 Pathogenic:1
Aug 24, 2017
OMIM
Significance:Pathogenic
Review Status:flagged submission
Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.084
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
18
DANN
Benign
0.88
DEOGEN2
Benign
0.044
T;T;T;T;.;.;T;T
Eigen
Benign
-0.37
Eigen_PC
Benign
-0.28
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.86
D;D;D;.;D;T;T;T
M_CAP
Benign
0.0098
T
MetaRNN
Benign
0.23
T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
2.0
M;.;.;M;.;.;.;.
PhyloP100
2.5
PrimateAI
Uncertain
0.58
T
PROVEAN
Benign
-0.99
N;.;.;.;.;.;.;.
REVEL
Benign
0.069
Sift
Benign
0.26
T;.;.;.;.;.;.;.
Sift4G
Benign
0.57
T;T;T;T;T;.;T;T
Polyphen
0.058
B;.;.;B;.;.;.;.
Vest4
0.25
MutPred
0.54
Gain of glycosylation at P167 (P = 0.2109);Gain of glycosylation at P167 (P = 0.2109);.;Gain of glycosylation at P167 (P = 0.2109);Gain of glycosylation at P167 (P = 0.2109);.;.;.;
MVP
0.41
MPC
0.18
ClinPred
0.28
T
GERP RS
2.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.17
gMVP
0.41
Mutation Taster
=1/99
disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs1555604710; hg19: chr17-73843922; API