Genetic Variant WBP2:p.Ala227Ala (chr17-75846959-G-A) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_012478.4(WBP2):c.681C>T(p.Ala227Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00601 in 1,614,114 control chromosomes in the GnomAD database, including 242 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 106 hom., cov: 32)

Exomes 𝑓: 0.0043 ( 136 hom. )

Consequence

WBP2
NM_012478.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.785

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 17-75846959-G-A is Benign according to our data. Variant chr17-75846959-G-A is described in ClinVar as [Benign]. Clinvar id is 1243088.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.785 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.065 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
WBP2	NM_012478.4 link	c.681C>T	p.Ala227Ala	synonymous_variant	Exon 7 of 8	ENST00000254806.8	NP_036610.2
WBP2	NM_001348170.1 link	c.681C>T	p.Ala227Ala	synonymous_variant	Exon 8 of 9		NP_001335099.1
WBP2	NM_001330499.2 link	c.546C>T	p.Ala182Ala	synonymous_variant	Exon 6 of 7		NP_001317428.1
WBP2	XM_047435712.1 link	c.615C>T	p.Ala205Ala	synonymous_variant	Exon 7 of 8		XP_047291668.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WBP2	ENST00000254806.8 link	c.681C>T	p.Ala227Ala	synonymous_variant	Exon 7 of 8	1	NM_012478.4	ENSP00000254806.3		Q969T9-1

Frequencies

GnomAD3 genomes

AF:

0.0222

AC:

3383

AN:

152154

Hom.:

106

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0672

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0202

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.0241

Gnomad SAS

AF:

0.0149

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000559

Gnomad OTH

AF:

0.0196

GnomAD3 exomes

AF:

0.0129

AC:

3231

AN:

251138

Hom.:

AF XY:

0.0109

AC XY:

1479

AN XY:

135826

show subpopulations

Gnomad AFR exome

AF:

0.0712

Gnomad AMR exome

AF:

0.0306

Gnomad ASJ exome

AF:

0.00189

Gnomad EAS exome

AF:

0.0232

Gnomad SAS exome

AF:

0.0142

Gnomad FIN exome

AF:

0.000786

Gnomad NFE exome

AF:

0.000643

Gnomad OTH exome

AF:

0.00734

GnomAD4 exome

AF:

0.00431

AC:

6307

AN:

1461842

Hom.:

136

Cov.:

AF XY:

0.00429

AC XY:

3122

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.0657

Gnomad4 AMR exome

AF:

0.0302

Gnomad4 ASJ exome

AF:

0.00241

Gnomad4 EAS exome

AF:

0.0163

Gnomad4 SAS exome

AF:

0.0133

Gnomad4 FIN exome

AF:

0.000974

Gnomad4 NFE exome

AF:

0.000290

Gnomad4 OTH exome

AF:

0.00833

GnomAD4 genome

AF:

0.0223

AC:

3389

AN:

152272

Hom.:

106

Cov.:

AF XY:

0.0219

AC XY:

1631

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0671

Gnomad4 AMR

AF:

0.0200

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.0242

Gnomad4 SAS

AF:

0.0152

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.000559

Gnomad4 OTH

AF:

0.0199

Alfa

AF:

0.0112

Hom.:

Bravo

AF:

0.0263

Asia WGS

AF:

0.0230

AC:

AN:

3478

EpiCase

AF:

0.000600

EpiControl

AF:

0.000593

ClinVar

Significance: Benign

Submissions summary: Benign:3

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

- -

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.44

CADD

Benign

9.6

DANN

Benign

0.93

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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