Genetic Variant WBP2:c.656-117T>C (chr17-75847101-A-G) – 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.656-117T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00475 in 1,128,564 control chromosomes in the GnomAD database, including 185 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 126 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 59 hom. )

Consequence

WBP2
NM_012478.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.981

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=-0.87).

BP6

Variant 17-75847101-A-G is Benign according to our data. Variant chr17-75847101-A-G is described in ClinVar as [Benign]. Clinvar id is 1224610.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0716 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
WBP2	NM_012478.4 link	c.656-117T>C	intron_variant	Intron 6 of 7	ENST00000254806.8	NP_036610.2
WBP2	NM_001348170.1 link	c.656-117T>C	intron_variant	Intron 7 of 8		NP_001335099.1
WBP2	NM_001330499.2 link	c.521-117T>C	intron_variant	Intron 5 of 6		NP_001317428.1
WBP2	XM_047435712.1 link	c.590-117T>C	intron_variant	Intron 6 of 7		XP_047291668.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WBP2	ENST00000254806.8 link	c.656-117T>C		intron_variant	Intron 6 of 7	1	NM_012478.4	ENSP00000254806.3		Q969T9-1

Frequencies

GnomAD3 genomes

AF:

0.0211

AC:

3211

AN:

152038

Hom.:

127

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0739

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00635

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.0177

GnomAD4 exome

AF:

0.00220

AC:

2148

AN:

976408

Hom.:

Cov.:

AF XY:

0.00181

AC XY:

902

AN XY:

497908

show subpopulations

Gnomad4 AFR exome

AF:

0.0743

Gnomad4 AMR exome

AF:

0.00341

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000130

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000109

Gnomad4 OTH exome

AF:

0.00484

GnomAD4 genome

AF:

0.0211

AC:

3212

AN:

152156

Hom.:

126

Cov.:

AF XY:

0.0206

AC XY:

1533

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.0737

Gnomad4 AMR

AF:

0.00634

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.0175

Alfa

AF:

0.0159

Hom.:

Bravo

AF:

0.0238

Asia WGS

AF:

0.00549

AC:

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

May 22, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.054

DANN

Benign

0.22

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