Genetic Variant WBP2:c.733-24G>A (chr17-75846811-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_012478.4(WBP2):c.733-24G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0944 in 1,586,868 control chromosomes in the GnomAD database, including 12,187 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 3420 hom., cov: 32)

Exomes 𝑓: 0.087 ( 8767 hom. )

Consequence

WBP2
NM_012478.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.616

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 17-75846811-C-T is Benign according to our data. Variant chr17-75846811-C-T is described in ClinVar as [Benign]. Clinvar id is 1239008.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
WBP2	NM_012478.4 link	c.733-24G>A	intron_variant	Intron 7 of 7	ENST00000254806.8	NP_036610.2
WBP2	NM_001348170.1 link	c.733-24G>A	intron_variant	Intron 8 of 8		NP_001335099.1
WBP2	NM_001330499.2 link	c.598-24G>A	intron_variant	Intron 6 of 6		NP_001317428.1
WBP2	XM_047435712.1 link	c.667-24G>A	intron_variant	Intron 7 of 7		XP_047291668.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WBP2	ENST00000254806.8 link	c.733-24G>A		intron_variant	Intron 7 of 7	1	NM_012478.4	ENSP00000254806.3		Q969T9-1

Frequencies

GnomAD3 genomes

AF:

0.164

AC:

24967

AN:

151964

Hom.:

3409

Cov.:

show subpopulations

Gnomad AFR

AF:

0.365

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.0943

Gnomad ASJ

AF:

0.112

Gnomad EAS

AF:

0.311

Gnomad SAS

AF:

0.158

Gnomad FIN

AF:

0.0528

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.0698

Gnomad OTH

AF:

0.158

GnomAD3 exomes

AF:

0.117

AC:

25487

AN:

218346

Hom.:

2481

AF XY:

0.115

AC XY:

13673

AN XY:

118480

show subpopulations

Gnomad AFR exome

AF:

0.370

Gnomad AMR exome

AF:

0.0556

Gnomad ASJ exome

AF:

0.110

Gnomad EAS exome

AF:

0.318

Gnomad SAS exome

AF:

0.159

Gnomad FIN exome

AF:

0.0513

Gnomad NFE exome

AF:

0.0682

Gnomad OTH exome

AF:

0.106

GnomAD4 exome

AF:

0.0870

AC:

124816

AN:

1434786

Hom.:

8767

Cov.:

AF XY:

0.0887

AC XY:

63071

AN XY:

710988

show subpopulations

Gnomad4 AFR exome

AF:

0.382

Gnomad4 AMR exome

AF:

0.0590

Gnomad4 ASJ exome

AF:

0.105

Gnomad4 EAS exome

AF:

0.325

Gnomad4 SAS exome

AF:

0.156

Gnomad4 FIN exome

AF:

0.0551

Gnomad4 NFE exome

AF:

0.0651

Gnomad4 OTH exome

AF:

0.110

GnomAD4 genome

AF:

0.164

AC:

25006

AN:

152082

Hom.:

3420

Cov.:

AF XY:

0.164

AC XY:

12219

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.365

Gnomad4 AMR

AF:

0.0942

Gnomad4 ASJ

AF:

0.112

Gnomad4 EAS

AF:

0.311

Gnomad4 SAS

AF:

0.159

Gnomad4 FIN

AF:

0.0528

Gnomad4 NFE

AF:

0.0698

Gnomad4 OTH

AF:

0.155

Alfa

AF:

0.0869

Hom.:

1488

Bravo

AF:

0.176

Asia WGS

AF:

0.216

AC:

750

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 16, 2021

GeneDx

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

-0.88

CADD

Benign

0.092

DANN

Benign

0.31

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