rs202022024

Variant names:

Variant summary

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

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. 13/22 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: 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

Publications

2 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

WBP2 links:

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=0.07531685).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
WBP2	NM_012478.4 link	c.478G>A	p.Ala160Thr	missense_variant	Exon 5 of 8	ENST00000254806.8	NP_036610.2
WBP2	NM_001348170.1 link	c.478G>A	p.Ala160Thr	missense_variant	Exon 6 of 9		NP_001335099.1
WBP2	XM_047435712.1 link	c.412G>A	p.Ala138Thr	missense_variant	Exon 5 of 8		XP_047291668.1
WBP2	NM_001330499.2 link	c.398-241G>A		intron_variant	Intron 4 of 6		NP_001317428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WBP2	ENST00000254806.8 link	c.478G>A	p.Ala160Thr	missense_variant	Exon 5 of 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

GnomAD2 exomes

AF:

0.0000245

AC:

AN:

163142

AF XY:

0.0000116

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 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

African (AFR)

AF:

0.00

AC:

AN:

31910

American (AMR)

AF:

0.000138

AC:

AN:

36274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25178

East Asian (EAS)

AF:

0.0000276

AC:

AN:

36210

South Asian (SAS)

AF:

0.00

AC:

AN:

79846

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49614

Middle Eastern (MID)

AF:

0.000175

AC:

AN:

5706

European-Non Finnish (NFE)

AF:

0.00000370

AC:

AN:

1082320

Other (OTH)

AF:

0.0000172

AC:

AN:

58266

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152030

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41432

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000388

AC:

AN:

5152

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67972

Other (OTH)

AF:

0.00

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

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

0.077

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

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;.;.;.;.

PhyloP100

4.5

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

Mutation Taster

=4/96

disease causing (ClinVar)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over