NM_024949.6:c.997G>C

Variant names:

• chr4-183253800-G-C
• rs1488760928
• NM_024949.6:c.997G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024949.6(WWC2):​c.997G>C​(p.Ala333Pro) variant causes a missense change. 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A333T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: WWC2 NM_024949.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.92
• Publications: 0 publications found

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

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=0.20001727).

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.997G>C	p.Ala333Pro	missense	Exon 9 of 23	NP_079225.5
	WWC2	NM_001410864.1		c.997G>C	p.Ala333Pro	missense	Exon 9 of 23	NP_001397793.1	Q6AWC2-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WWC2	ENST00000403733.8	TSL:5 MANE Select	c.997G>C	p.Ala333Pro	missense	Exon 9 of 23	ENSP00000384222.3	Q6AWC2-1
	WWC2	ENST00000962606.1		c.997G>C	p.Ala333Pro	missense	Exon 9 of 23	ENSP00000632665.1
	WWC2	ENST00000448232.6	TSL:5	c.997G>C	p.Ala333Pro	missense	Exon 9 of 23	ENSP00000398577.2	Q6AWC2-6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.032	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		3.9
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.049
Sift	Benign	0.035	D
Sift4G	Benign	0.11	T
Polyphen		0.041	B
Vest4		0.32
MutPred		0.27		Gain of glycosylation at S331 (P = 0.0269)
MVP		0.28
MPC		0.035
ClinPred		0.52	D
GERP RS		1.6
Varity_R		0.24
gMVP		0.28
Mutation Taster		=70/30	polymorphism

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

Other links and lift over

dbSNP: rs1488760928; hg19: chr4-184174953;