Variant rs202022024 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP5BP4

The NM_012478.4(WBP2):c.478G>A(p.Ala160Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000899 in 1,557,354 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000085 ( 0 hom. )

Consequence

WBP2
NM_012478.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.54

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 links:

WBP2 (HGNC:):

WBP2 links:

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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 17-75847850-C-T is Pathogenic according to our data. Variant chr17-75847850-C-T is described in ClinVar as [no_classifications_from_unflagged_records]. Clinvar id is 437831.We mark this variant Likely_pathogenic, oryginal submissions are: {Pathogenic=1}.

BP4

Computational evidence support a benign effect (MetaRNN=0.07531685). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
WBP2	NM_012478.4 linkuse as main transcript	c.478G>A	p.Ala160Thr	missense_variant	5/8	ENST00000254806.8	NP_036610.2
WBP2	NM_001348170.1 linkuse as main transcript	c.478G>A	p.Ala160Thr	missense_variant	6/9		NP_001335099.1
WBP2	XM_047435712.1 linkuse as main transcript	c.412G>A	p.Ala138Thr	missense_variant	5/8		XP_047291668.1
WBP2	NM_001330499.2 linkuse as main transcript	c.398-241G>A		intron_variant			NP_001317428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WBP2	ENST00000254806.8 linkuse as main transcript	c.478G>A	p.Ala160Thr	missense_variant	5/8	1	NM_012478.4	ENSP00000254806.3		Q969T9-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151912

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000387

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000245

AC:

AN:

163142

Hom.:

AF XY:

0.0000116

AC XY:

AN XY:

86260

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000119

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000840

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000854

AC:

AN:

1405324

Hom.:

Cov.:

AF XY:

0.00000721

AC XY:

AN XY:

693766

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000138

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000276

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000370

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152030

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000388

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000843

Hom.:

Bravo

AF:

0.0000264

ESP6500AA

AF:

0.000230

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000174

AC:

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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.041

T;T;T;T;.;.;T;T

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.035

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.86

D;D;D;.;D;D;T;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.075

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.93

L;.;.;L;.;.;.;.

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.0

N;.;.;.;.;.;.;.

REVEL

Benign

0.058

Sift

Benign

0.23

T;.;.;.;.;.;.;.

Sift4G

Benign

0.45

T;T;T;T;T;.;T;T

Polyphen

0.016

B;.;.;B;.;.;.;.

Vest4

0.80

MVP

0.56

MPC

0.19

ClinPred

0.19

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.10

gMVP

0.65

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over