Variant chr17-75846969-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5

The NM_012478.4(WBP2):c.671C>T(p.Ala224Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,836 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as no classifications from unflagged records (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

WBP2
NM_012478.4 missense

Scores

Clinical Significance

no classifications from unflagged records no classifications from unflagged records P:1

Conservation

PhyloP100: 6.43

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:

WBP2 (HGNC:):

WBP2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 17-75846969-G-A is Pathogenic according to our data. Variant chr17-75846969-G-A is described in ClinVar as [no_classifications_from_unflagged_records]. Clinvar id is 437832.We mark this variant Likely_pathogenic, oryginal submissions are: {Pathogenic=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
WBP2	NM_012478.4 linkuse as main transcript	c.671C>T	p.Ala224Val	missense_variant	7/8	ENST00000254806.8	NP_036610.2
WBP2	NM_001348170.1 linkuse as main transcript	c.671C>T	p.Ala224Val	missense_variant	8/9		NP_001335099.1
WBP2	NM_001330499.2 linkuse as main transcript	c.536C>T	p.Ala179Val	missense_variant	6/7		NP_001317428.1
WBP2	XM_047435712.1 linkuse as main transcript	c.605C>T	p.Ala202Val	missense_variant	7/8		XP_047291668.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WBP2	ENST00000254806.8 linkuse as main transcript	c.671C>T	p.Ala224Val	missense_variant	7/8	1	NM_012478.4	ENSP00000254806.3		Q969T9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461836

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727222

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: no classifications from unflagged records

Submissions summary: Pathogenic:1

Revision: no classifications from unflagged records

LINK: link

Submissions by phenotype

Hearing loss, autosomal recessive 107

Pathogenic:1

Pathogenic, flagged submission

literature only

OMIM

Aug 24, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Benign

-0.031

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.079

T;T;T;.;.

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.87

D;D;.;D;D

M_CAP

Benign

0.055

MetaRNN

Uncertain

0.61

D;D;D;D;D

MetaSVM

Benign

-0.60

MutationAssessor

Uncertain

2.5

M;.;M;.;.

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-1.6

N;.;.;.;N

REVEL

Benign

0.11

Sift

Uncertain

0.022

D;.;.;.;T

Sift4G

Benign

0.075

T;T;T;T;T

Polyphen

0.58

P;.;P;.;.

Vest4

0.88

MutPred

0.39

Loss of phosphorylation at S229 (P = 0.1633);.;Loss of phosphorylation at S229 (P = 0.1633);.;.;

MVP

0.67

MPC

0.44

ClinPred

0.97

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.23

gMVP

0.62

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

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