Variant 4-183240212-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024949.6(WWC2):c.552G>T(p.Gln184His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000387 in 1,552,030 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

WWC2
NM_024949.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0750

Variant links:

Genes affected

WWC2 (HGNC:24148): (WW and C2 domain containing 2) This gene encodes a member of the WW-and-C2-domain-containing family of proteins. Members of this family have two N-terminal WW domains that mediate binding to target proteins harboring L/PPxY motifs, an internal C2 domain for membrane association, and C-terminal alpha protein kinase C binding sites and class III PDZ domain-interaction motifs. Proteins of this family are able to form homo- and heterodimers and to modulate hippo pathway signaling. [provided by RefSeq, Sep 2016]

WWC2 links:

WWC2-AS1 (HGNC:):

WWC2-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12886012).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WWC2	NM_024949.6 linkuse as main transcript	c.552G>T	p.Gln184His	missense_variant	5/23	ENST00000403733.8	NP_079225.5	Q6AWC2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WWC2	ENST00000403733.8 linkuse as main transcript	c.552G>T	p.Gln184His	missense_variant	5/23	5	NM_024949.6	ENSP00000384222.3		Q6AWC2-1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000249

AC:

AN:

160372

Hom.:

AF XY:

0.0000238

AC XY:

AN XY:

84106

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:

0.0000627

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000379

AC:

AN:

1399788

Hom.:

Cov.:

AF XY:

0.0000377

AC XY:

AN XY:

690428

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:

0.0000491

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000761

Hom.:

Bravo

AF:

0.0000453

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

Jul 30, 2024

The c.552G>T (p.Q184H) alteration is located in exon 5 (coding exon 5) of the WWC2 gene. This alteration results from a G to T substitution at nucleotide position 552, causing the glutamine (Q) at amino acid position 184 to be replaced by a histidine (H). 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

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0072

T;.;.

Eigen

Benign

-0.00036

Eigen_PC

Benign

-0.035

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.72

T;T;T

M_CAP

Benign

0.0063

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;L;L

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-2.0

N;N;N

REVEL

Benign

0.11

Sift

Benign

0.46

T;T;T

Sift4G

Benign

0.25

T;T;T

Polyphen

1.0

D;.;.

Vest4

0.20

MutPred

0.27

Gain of glycosylation at S183 (P = 0.0014);Gain of glycosylation at S183 (P = 0.0014);Gain of glycosylation at S183 (P = 0.0014);

MVP

0.49

MPC

0.030

ClinPred

0.13

GERP RS

0.60

Varity_R

0.044

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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