rs1555604710
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP5BP4
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. 14/21 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
NM_012478.4 missense
Scores
1
2
16
Clinical Significance
Conservation
PhyloP100: 2.50
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 17-75847841-T-G is Pathogenic according to our data. Variant chr17-75847841-T-G is described in ClinVar as [no_classifications_from_unflagged_records]. Clinvar id is 437833.We mark this variant Likely_pathogenic, oryginal submissions are: {Pathogenic=1}.
BP4
Computational evidence support a benign effect (MetaRNN=0.2271018). . Strength limited to SUPPORTING due to the PP5.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
WBP2 | NM_012478.4 | c.487A>C | p.Met163Leu | missense_variant | 5/8 | ENST00000254806.8 | NP_036610.2 | |
WBP2 | NM_001348170.1 | c.487A>C | p.Met163Leu | missense_variant | 6/9 | NP_001335099.1 | ||
WBP2 | XM_047435712.1 | c.421A>C | p.Met141Leu | missense_variant | 5/8 | XP_047291668.1 | ||
WBP2 | NM_001330499.2 | c.398-232A>C | intron_variant | NP_001317428.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
WBP2 | ENST00000254806.8 | c.487A>C | p.Met163Leu | missense_variant | 5/8 | 1 | NM_012478.4 | ENSP00000254806 | P4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome 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
Pathogenic, flagged submission | literature only | OMIM | Aug 24, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;T;T;T;.;.;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;.;D;T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
M;.;.;M;.;.;.;.
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;.;.;.;.;.;.
REVEL
Benign
Sift
Benign
T;.;.;.;.;.;.;.
Sift4G
Benign
T;T;T;T;T;.;T;T
Polyphen
B;.;.;B;.;.;.;.
Vest4
MutPred
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
MPC
0.18
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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