WWC2

protein-coding

WW and C2 domain containing 2, the group of WWC family|C2 and WW domain containing

Gene summary

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]

MANE transcript

NM_024949.6

Inheritance

—

ClinVar variants

U:169B:10

Top phenotype

Long QT syndrome

gnomAD constraint

pLI —, LoF o/e 0.39

Max pathogenic AF

—

Genomic locus

chr4:183,099,257-183,320,777

External References & Databases

Ensembl (ENSG00000151718)

Transcript & Mutation Effects

hg38 • Region Span ~221.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to WWC2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 164

not providedTotal: 4

Long QT syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_024949.6. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	2 clinvar	2 clinvar	5
missense			163 clinvar	6 clinvar		169
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	169	8	2	179

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 45 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_024949.6	RefSeq	NP_079225.5	23	MANE Select
ENST00000403733.8	Ensembl	ENSP00000384222.3	23	MANE Select
NM_001410864.1	RefSeq	NP_001397793.1	23	Standard
ENST00000427431.5	Ensembl	ENSP00000393342.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

negative regulation of transcription by RNA polymerase II
negative regulation of hippo signaling
negative regulation of organ growth

Molecular Function

kinase binding
protein-containing complex scaffold activity

Cellular Component

cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000403733
Coding exons: 23
Length: 221485
Individuals with no LoFs: 125544
Homozygous LoFs: 0
Heterozygous LoFs: 49
Defined: 125593
p: 0.000195

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.342	574	597	0.961	0.0000317	7698
Missense (PolyPhen)		185	215.26	0.85941		2771
Synonymous	-0.465	242	233	1.04	0.0000127	2278
Loss of Function	4.27	22	56.7	0.388	0.00000266	775

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.00039	0.00038	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00017	0.00016	rare
Finnish	0.00023	0.00023	rare
European (Non-Finnish)	0.00014	0.00014	rare
South Asian	0.00024	0.00023	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.0950

Intolerance Scores

LoFtool: 0.910
RVIS EVS: 0.06
RVIS percentile EVS: 57.55

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.714

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium