chr17-75847528-T-C
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_012478.4(WBP2):āc.614A>Gā(p.Glu205Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000693 in 1,442,150 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 6.9e-7 ( 0 hom. )
Consequence
WBP2
NM_012478.4 missense
NM_012478.4 missense
Scores
5
14
Clinical Significance
Conservation
PhyloP100: 6.30
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3576485).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WBP2 | NM_012478.4 | c.614A>G | p.Glu205Gly | missense_variant | 6/8 | ENST00000254806.8 | |
WBP2 | NM_001348170.1 | c.614A>G | p.Glu205Gly | missense_variant | 7/9 | ||
WBP2 | NM_001330499.2 | c.479A>G | p.Glu160Gly | missense_variant | 5/7 | ||
WBP2 | XM_047435712.1 | c.548A>G | p.Glu183Gly | missense_variant | 6/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WBP2 | ENST00000254806.8 | c.614A>G | p.Glu205Gly | missense_variant | 6/8 | 1 | NM_012478.4 | P4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.93e-7 AC: 1AN: 1442150Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 716034
GnomAD4 exome
AF:
AC:
1
AN:
1442150
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
716034
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 14, 2023 | This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 205 of the WBP2 protein (p.Glu205Gly). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt WBP2 protein function. This variant has not been reported in the literature in individuals affected with WBP2-related conditions. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;T;T;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;D;T;.;T;T;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.;L;.;.;.
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;.;.;.;N;.
REVEL
Benign
Sift
Benign
T;.;.;.;.;T;.
Sift4G
Benign
T;T;T;T;T;T;.
Polyphen
D;.;.;D;.;.;.
Vest4
MutPred
Loss of glycosylation at P203 (P = 0.1062);Loss of glycosylation at P203 (P = 0.1062);.;Loss of glycosylation at P203 (P = 0.1062);.;.;.;
MVP
MPC
0.48
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.