4-183099499-G-C

Variant names:

• chr4-183099499-G-C
• NM_024949.6:c.8G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

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 𝑓: 0.0000025 (0 hom.)
• Consequence: WWC2 NM_024949.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.67

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]

ACMG classification

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
WWC2	NM_024949.6	c.8G>C	p.Arg3Thr	missense_variant	Exon 1 of 23	ENST00000403733.8	NP_079225.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WWC2	ENST00000403733.8	c.8G>C	p.Arg3Thr	missense_variant	Exon 1 of 23	5	NM_024949.6	ENSP00000384222.3
WWC2	ENST00000448232.6	c.8G>C	p.Arg3Thr	missense_variant	Exon 1 of 23	5		ENSP00000398577.2
WWC2	ENST00000513834.5	c.8G>C	p.Arg3Thr	missense_variant	Exon 1 of 23	5		ENSP00000425054.1
WWC2	ENST00000508614.5	n.8G>C		non_coding_transcript_exon_variant	Exon 1 of 4	3		ENSP00000423238.1

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

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;