Genetic Variant WBP2:p.Pro255Pro (chr17-75846755-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_012478.4(WBP2):c.765G>A(p.Pro255Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000665 in 1,534,268 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000061 ( 0 hom. )

Consequence

WBP2
NM_012478.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.848

Publications

0 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
Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, ClinGen
hearing loss, autosomal recessive 107
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

WBP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.013841718).

BP6

Variant 17-75846755-C-T is Benign according to our data. Variant chr17-75846755-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1612091.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.848 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012478.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WBP2	NM_012478.4	MANE Select	c.765G>A	p.Pro255Pro	synonymous	Exon 8 of 8	NP_036610.2
WBP2	NM_001348170.1		c.765G>A	p.Pro255Pro	synonymous	Exon 9 of 9	NP_001335099.1	Q969T9-1
WBP2	NM_001330499.2		c.630G>A	p.Pro210Pro	synonymous	Exon 7 of 7	NP_001317428.1	Q969T9-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WBP2	ENST00000254806.8	TSL:1 MANE Select	c.765G>A	p.Pro255Pro	synonymous	Exon 8 of 8	ENSP00000254806.3	Q969T9-1
WBP2	ENST00000626827.2	TSL:5	c.688G>A	p.Gly230Arg	missense	Exon 7 of 7	ENSP00000486675.1	K7ENL2
WBP2	ENST00000591399.5	TSL:5	c.765G>A	p.Pro255Pro	synonymous	Exon 9 of 9	ENSP00000467579.1	Q969T9-1

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

151968

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00433

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000701

AC:

AN:

156878

AF XY:

0.0000364

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00204

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000615

AC:

AN:

1382300

Hom.:

Cov.:

AF XY:

0.0000515

AC XY:

AN XY:

679612

show subpopulations

African (AFR)

AF:

0.0000319

AC:

AN:

31306

American (AMR)

AF:

0.00

AC:

AN:

33706

Ashkenazi Jewish (ASJ)

AF:

0.00248

AC:

AN:

22146

East Asian (EAS)

AF:

0.00

AC:

AN:

37378

South Asian (SAS)

AF:

0.0000135

AC:

AN:

74246

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49298

Middle Eastern (MID)

AF:

0.000182

AC:

AN:

5490

European-Non Finnish (NFE)

AF:

0.0000149

AC:

AN:

1071578

Other (OTH)

AF:

0.000192

AC:

AN:

57152

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000112

AC:

AN:

151968

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74202

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41382

American (AMR)

AF:

0.0000655

AC:

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.00433

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5148

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0000943

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67978

Other (OTH)

AF:

0.00

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000314

Hom.:

Bravo

AF:

0.0000756

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.0000665

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.40

CADD

Benign

5.7

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.021

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.53

MetaRNN

Benign

0.014

PhyloP100

-0.85

Sift4G

Uncertain

0.0070

Vest4

0.20

MVP

0.088

ClinPred

0.077

GERP RS

-7.7

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over