rs2290771

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_012478.4(WBP2):c.305-5T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 1,610,644 control chromosomes in the GnomAD database, including 103,185 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 19950 hom., cov: 33)

Exomes 𝑓: 0.32 ( 83235 hom. )

Consequence

WBP2
NM_012478.4 splice_region, intron

Scores

Splicing: ADA: 0.00004055

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.46

Publications

28 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: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 17-75848667-A-G is Benign according to our data. Variant chr17-75848667-A-G is described in ClinVar as Benign. ClinVar VariationId is 1264383.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.82 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
WBP2	NM_012478.4 link	c.305-5T>C	splice_region_variant, intron_variant	Intron 3 of 7	ENST00000254806.8	NP_036610.2
WBP2	NM_001348170.1 link	c.305-5T>C	splice_region_variant, intron_variant	Intron 4 of 8		NP_001335099.1
WBP2	NM_001330499.2 link	c.305-5T>C	splice_region_variant, intron_variant	Intron 3 of 6		NP_001317428.1
WBP2	XM_047435712.1 link	c.239-5T>C	splice_region_variant, intron_variant	Intron 3 of 7		XP_047291668.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WBP2	ENST00000254806.8 link	c.305-5T>C		splice_region_variant, intron_variant	Intron 3 of 7	1	NM_012478.4	ENSP00000254806.3		Q969T9-1

Frequencies

GnomAD3 genomes

AF:

0.452

AC:

68700

AN:

151972

Hom.:

19889

Cov.:

show subpopulations

Gnomad AFR

AF:

0.828

Gnomad AMI

AF:

0.293

Gnomad AMR

AF:

0.343

Gnomad ASJ

AF:

0.404

Gnomad EAS

AF:

0.145

Gnomad SAS

AF:

0.344

Gnomad FIN

AF:

0.215

Gnomad MID

AF:

0.456

Gnomad NFE

AF:

0.321

Gnomad OTH

AF:

0.443

GnomAD2 exomes

AF:

0.332

AC:

82186

AN:

247894

AF XY:

0.329

show subpopulations

Gnomad AFR exome

AF:

0.844

Gnomad AMR exome

AF:

0.276

Gnomad ASJ exome

AF:

0.386

Gnomad EAS exome

AF:

0.140

Gnomad FIN exome

AF:

0.215

Gnomad NFE exome

AF:

0.317

Gnomad OTH exome

AF:

0.341

GnomAD4 exome

AF:

0.324

AC:

473019

AN:

1458554

Hom.:

83235

Cov.:

AF XY:

0.325

AC XY:

235674

AN XY:

725560

show subpopulations

African (AFR)

AF:

0.850

AC:

28362

AN:

33372

American (AMR)

AF:

0.284

AC:

12639

AN:

44522

Ashkenazi Jewish (ASJ)

AF:

0.389

AC:

10149

AN:

26086

East Asian (EAS)

AF:

0.153

AC:

6072

AN:

39630

South Asian (SAS)

AF:

0.356

AC:

30631

AN:

85960

European-Finnish (FIN)

AF:

0.220

AC:

11699

AN:

53178

Middle Eastern (MID)

AF:

0.494

AC:

2842

AN:

5758

European-Non Finnish (NFE)

AF:

0.315

AC:

349338

AN:

1109778

Other (OTH)

AF:

0.353

AC:

21287

AN:

60270

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

15996

31991

47987

63982

79978

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11576

23152

34728

46304

57880

<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:

0.452

AC:

68820

AN:

152090

Hom.:

19950

Cov.:

AF XY:

0.442

AC XY:

32893

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.828

AC:

34351

AN:

41496

American (AMR)

AF:

0.342

AC:

5224

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.404

AC:

1401

AN:

3468

East Asian (EAS)

AF:

0.146

AC:

752

AN:

5162

South Asian (SAS)

AF:

0.345

AC:

1660

AN:

4818

European-Finnish (FIN)

AF:

0.215

AC:

2277

AN:

10590

Middle Eastern (MID)

AF:

0.452

AC:

133

AN:

294

European-Non Finnish (NFE)

AF:

0.321

AC:

21805

AN:

67958

Other (OTH)

AF:

0.449

AC:

950

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1545

3091

4636

6182

7727

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

562

1124

1686

2248

2810

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.359

Hom.:

8735

Bravo

AF:

0.478

Asia WGS

AF:

0.315

AC:

1096

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 05, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hearing loss, autosomal recessive 107

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

5.4

(source)

DANN

Benign

0.56

PhyloP100

1.5

PromoterAI

-0.086

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000041

dbscSNV1_RF

Benign

0.0040

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over