4-183099499-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_024949.6(WWC2):​c.8G>C​(p.Arg3Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000249 in 1,203,266 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000025 ( 0 hom. )

Consequence

WWC2
NM_024949.6 missense

Scores

3
3
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.67
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.32320192).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
WWC2NM_024949.6 linkc.8G>C p.Arg3Thr missense_variant Exon 1 of 23 ENST00000403733.8 NP_079225.5 Q6AWC2-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
WWC2ENST00000403733.8 linkc.8G>C p.Arg3Thr missense_variant Exon 1 of 23 5 NM_024949.6 ENSP00000384222.3 Q6AWC2-1
WWC2ENST00000448232.6 linkc.8G>C p.Arg3Thr missense_variant Exon 1 of 23 5 ENSP00000398577.2 Q6AWC2-6
WWC2ENST00000513834.5 linkc.8G>C p.Arg3Thr missense_variant Exon 1 of 23 5 ENSP00000425054.1 Q6AWC2-4
WWC2ENST00000508614.5 linkn.8G>C non_coding_transcript_exon_variant Exon 1 of 4 3 ENSP00000423238.1 D6R9P8

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000249
AC:
3
AN:
1203266
Hom.:
0
Cov.:
30
AF XY:
0.00000509
AC XY:
3
AN XY:
589784
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:
0.00000309
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.72
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.46
CADD
Uncertain
25
DANN
Benign
0.95
DEOGEN2
Benign
0.015
T;.;.
Eigen
Benign
0.12
Eigen_PC
Benign
0.17
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Benign
0.63
T;T;T
M_CAP
Pathogenic
0.61
D
MetaRNN
Benign
0.32
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.7
L;L;L
PrimateAI
Pathogenic
0.93
D
PROVEAN
Benign
-2.3
N;N;N
REVEL
Benign
0.13
Sift
Uncertain
0.0020
D;D;D
Sift4G
Uncertain
0.0060
D;D;D
Polyphen
0.60
P;.;.
Vest4
0.42
MutPred
0.30
Loss of MoRF binding (P = 0.0085);Loss of MoRF binding (P = 0.0085);Loss of MoRF binding (P = 0.0085);
MVP
0.33
MPC
0.26
ClinPred
0.88
D
GERP RS
3.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.47
gMVP
0.21

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-184020652; API