Variant 17-75847522-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_012478.4(WBP2):c.620C>T(p.Pro207Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000278 in 1,440,568 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

WBP2
NM_012478.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.10

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
WBP2	NM_012478.4 linkuse as main transcript	c.620C>T	p.Pro207Leu	missense_variant	6/8	ENST00000254806.8
WBP2	NM_001348170.1 linkuse as main transcript	c.620C>T	p.Pro207Leu	missense_variant	7/9
WBP2	NM_001330499.2 linkuse as main transcript	c.485C>T	p.Pro162Leu	missense_variant	5/7
WBP2	XM_047435712.1 linkuse as main transcript	c.554C>T	p.Pro185Leu	missense_variant	6/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WBP2	ENST00000254806.8 linkuse as main transcript	c.620C>T	p.Pro207Leu	missense_variant	6/8	1	NM_012478.4	P4	Q969T9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000437

AC:

AN:

228680

Hom.:

AF XY:

0.00

AC XY:

AN XY:

124396

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000969

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000278

AC:

AN:

1440568

Hom.:

Cov.:

AF XY:

0.00000419

AC XY:

AN XY:

715196

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000363

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 22, 2023

The c.620C>T (p.P207L) alteration is located in exon 6 (coding exon 6) of the WBP2 gene. This alteration results from a C to T substitution at nucleotide position 620, causing the proline (P) at amino acid position 207 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.070

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.21

T;T;T;T;.;.;.

Eigen

Benign

0.019

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.80

T;T;T;.;T;T;T

M_CAP

Pathogenic

0.30

MetaRNN

Uncertain

0.50

T;T;T;T;T;T;T

MetaSVM

Uncertain

0.24

MutationAssessor

Benign

0.81

L;.;.;L;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Uncertain

0.74

PROVEAN

Pathogenic

-4.9

D;.;.;.;.;D;.

REVEL

Benign

0.21

Sift

Uncertain

0.0020

D;.;.;.;.;D;.

Sift4G

Benign

0.16

T;T;T;T;T;T;.

Polyphen

0.020

B;.;.;B;.;.;.

Vest4

0.65

MutPred

0.24

Gain of sheet (P = 0.0507);Gain of sheet (P = 0.0507);.;Gain of sheet (P = 0.0507);.;.;.;

MVP

0.92

MPC

0.20

ClinPred

0.77

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.38

gMVP

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

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