rs1453270147

Variant names:

• chr4-183099615-C-G
• rs1453270147
• NM_024949.6:c.124C>G

Your query was ambiguous. Multiple possible variants found:

• chr4-183099615-C-G
• chr4-183099615-C-T

Variant summary

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

The NM_024949.6(WWC2):​c.124C>G​(p.Arg42Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,360,504 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: WWC2 NM_024949.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.62
• Publications: 1 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.124C>G	p.Arg42Gly	missense	Exon 1 of 23	NP_079225.5
	WWC2	NM_001410864.1		c.124C>G	p.Arg42Gly	missense	Exon 1 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.124C>G	p.Arg42Gly	missense	Exon 1 of 23	ENSP00000384222.3	Q6AWC2-1
	WWC2	ENST00000962606.1		c.124C>G	p.Arg42Gly	missense	Exon 1 of 23	ENSP00000632665.1
	WWC2	ENST00000448232.6	TSL:5	c.124C>G	p.Arg42Gly	missense	Exon 1 of 23	ENSP00000398577.2	Q6AWC2-6

Frequencies

GnomAD3 genomes AF: 0.00000662 AC: 1 AN: 151140 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000111 AC: 1 AN: 89776 AF XY: 0.0000201

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000333

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000124 AC: 15 AN: 1209364 Hom.: 0 Cov.: 30 AF XY: 0.0000135 AC XY: 8 AN XY: 592794

African (AFR) AF: 0.00 AC: 0 AN: 24758

American (AMR) AF: 0.0000417 AC: 1 AN: 23964

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19058

East Asian (EAS) AF: 0.00 AC: 0 AN: 24284

South Asian (SAS) AF: 0.00 AC: 0 AN: 53722

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40808

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4810

European-Non Finnish (NFE) AF: 0.0000144 AC: 14 AN: 970848

Other (OTH) AF: 0.00 AC: 0 AN: 47112

GnomAD4 genome AF: 0.00000662 AC: 1 AN: 151140 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 73792

African (AFR) AF: 0.0000242 AC: 1 AN: 41358

American (AMR) AF: 0.00 AC: 0 AN: 15174

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 5132

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10214

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67668

Other (OTH) AF: 0.00 AC: 0 AN: 2076

Alfa AF: 0.0000313 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	25
DANN	Benign	0.96
DEOGEN2	Uncertain	0.73	D
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.50	N
LIST_S2	Uncertain	0.96	D
M_CAP	Pathogenic	0.88	D
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		1.6
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-3.2	D
REVEL	Uncertain	0.31
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.68	P
Vest4		0.58
MutPred		0.53		Gain of glycosylation at T46 (P = 0.0053)
MVP		0.43
MPC		0.042
ClinPred		0.51	D
GERP RS		2.0
PromoterAI		-0.014	Neutral
Varity_R		0.35
gMVP		0.38
Mutation Taster		=69/31	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: rs1453270147; hg19: chr4-184020768;