rs2290771

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_012478.4(WBP2):c.305-5T>C variant causes a splice region, splice polypyrimidine tract, 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, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00004055

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.46

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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	MANE
WBP2	NM_012478.4 linkuse as main transcript	c.305-5T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000254806.8
WBP2	NM_001330499.2 linkuse as main transcript	c.305-5T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
WBP2	NM_001348170.1 linkuse as main transcript	c.305-5T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
WBP2	XM_047435712.1 linkuse as main transcript	c.239-5T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WBP2	ENST00000254806.8 linkuse as main transcript	c.305-5T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_012478.4	P4	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

GnomAD3 exomes

AF:

0.332

AC:

82186

AN:

247894

Hom.:

16315

AF XY:

0.329

AC XY:

44145

AN XY:

134024

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 SAS exome

AF:

0.359

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

Gnomad4 AFR exome

AF:

0.850

Gnomad4 AMR exome

AF:

0.284

Gnomad4 ASJ exome

AF:

0.389

Gnomad4 EAS exome

AF:

0.153

Gnomad4 SAS exome

AF:

0.356

Gnomad4 FIN exome

AF:

0.220

Gnomad4 NFE exome

AF:

0.315

Gnomad4 OTH exome

AF:

0.353

GnomAD4 genome

AF:

0.452

AC:

68820

AN:

152090

Hom.:

19950

Cov.:

AF XY:

0.442

AC XY:

32893

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.828

Gnomad4 AMR

AF:

0.342

Gnomad4 ASJ

AF:

0.404

Gnomad4 EAS

AF:

0.146

Gnomad4 SAS

AF:

0.345

Gnomad4 FIN

AF:

0.215

Gnomad4 NFE

AF:

0.321

Gnomad4 OTH

AF:

0.449

Alfa

AF:

0.352

Hom.:

7544

Bravo

AF:

0.478

Asia WGS

AF:

0.315

AC:

1096

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -

Hearing loss, autosomal recessive 107

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

Cadd

Benign

5.4

Dann

Benign

0.56

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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