Variant chr4-183253796-T-G 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.993T>G(p.Ser331Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,380 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

WWC2
NM_024949.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.600

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:

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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=0.245316).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WWC2	NM_024949.6 linkuse as main transcript	c.993T>G	p.Ser331Arg	missense_variant	9/23	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.993T>G	p.Ser331Arg	missense_variant	9/23	5	NM_024949.6	ENSP00000384222.3		Q6AWC2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461380

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726946

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:

0.0000166

GnomAD4 genome

Cov.:

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

Mar 29, 2024

The c.993T>G (p.S331R) alteration is located in exon 9 (coding exon 9) of the WWC2 gene. This alteration results from a T to G substitution at nucleotide position 993, causing the serine (S) at amino acid position 331 to be replaced by an arginine (R). 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

0.33

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.098

T;.;.;.

Eigen

Benign

0.0099

Eigen_PC

Benign

0.036

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.88

D;D;D;T

M_CAP

Benign

0.0087

MetaRNN

Benign

0.25

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

M;M;M;.

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-2.6

D;D;D;D

REVEL

Benign

0.070

Sift

Uncertain

0.0080

D;D;D;D

Sift4G

Uncertain

0.027

D;D;D;D

Polyphen

0.81

P;.;.;.

Vest4

0.48

MutPred

0.23

Gain of glycosylation at S331 (P = 0.0269);Gain of glycosylation at S331 (P = 0.0269);Gain of glycosylation at S331 (P = 0.0269);.;

MVP

0.31

MPC

0.062

ClinPred

0.93

GERP RS

1.9

Varity_R

0.15

gMVP

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over