Genetic Variant NM_024949.6:c.19A>G (chr4-183099510-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024949.6(WWC2):c.19A>G(p.Ser7Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

WWC2
NM_024949.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.881

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14025089).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024949.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WWC2	NM_024949.6	MANE Select	c.19A>G	p.Ser7Gly	missense	Exon 1 of 23	NP_079225.5
	WWC2	NM_001410864.1		c.19A>G	p.Ser7Gly	missense	Exon 1 of 23	NP_001397793.1	Q6AWC2-6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WWC2	ENST00000403733.8	TSL:5 MANE Select	c.19A>G	p.Ser7Gly	missense	Exon 1 of 23	ENSP00000384222.3	Q6AWC2-1
WWC2	ENST00000962606.1		c.19A>G	p.Ser7Gly	missense	Exon 1 of 23	ENSP00000632665.1
WWC2	ENST00000448232.6	TSL:5	c.19A>G	p.Ser7Gly	missense	Exon 1 of 23	ENSP00000398577.2	Q6AWC2-6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1236380

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

607710

African (AFR)

AF:

0.00

AC:

AN:

25114

American (AMR)

AF:

0.00

AC:

AN:

25296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19722

East Asian (EAS)

AF:

0.00

AC:

AN:

25452

South Asian (SAS)

AF:

0.00

AC:

AN:

59042

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42082

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4806

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

986344

Other (OTH)

AF:

0.00

AC:

AN:

48522

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Uncertain

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.0017

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.59

M_CAP

Pathogenic

0.52

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

0.88

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.90

REVEL

Benign

0.0090

Sift

Uncertain

0.024

Sift4G

Uncertain

0.060

Polyphen

0.012

Vest4

0.11

MutPred

0.31

Loss of helix (P = 0.0167)

MVP

0.15

MPC

0.030

ClinPred

0.22

GERP RS

1.9

PromoterAI

-0.12

Neutral

(source)

Varity_R

0.23

gMVP

0.083

Mutation Taster

=92/8

polymorphism

(source)

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over