WFDC2

protein-coding

WAP four-disulfide core domain 2, the group of WAP four-disulfide core domain containing

Gene summary

This gene encodes a protein that is a member of the WFDC domain family. The WFDC domain, or WAP Signature motif, contains eight cysteines forming four disulfide bonds at the core of the protein, and functions as a protease inhibitor in many family members. This gene is expressed in pulmonary epithelial cells, and was also found to be expressed in some ovarian cancers. The encoded protein is a small secretory protein, which may be involved in sperm maturation. [provided by RefSeq, Jul 2008]

MANE transcript

NM_006103.4

Inheritance

ClinVar variants

P:3U:25B:2

Top phenotype

Bronchiectasis and nasal polyposis

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr20:45,469,753-45,481,532

External References & Databases

Ensembl (ENSG00000101443)

Transcript & Mutation Effects

hg38 • Region Span ~11.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

bronchiectasis and nasal polyposisSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0975835

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Bronchiectasis and nasal polyposisAR

Manifestation: Allergy/Immunology/Infectious; Obstetric; Pulmonary

Intervention: Allergy/Immunology/Infectious; Pulmonary

Rationale: The condition involves chronic airway infections resulting in pulmonary and related sequelae, and diagnosis may allow interventions to prevent and treat infections as well as optimize pulmonary function; lung transplant has been described

Refs: 38626355

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to WFDC2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 23

Bronchiectasis and nasal polyposisTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006103.4. 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						0
missense		2 clinvar	22 clinvar	2 clinvar		26
nonsense						0
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	1	2	25	2	0	30

Highest pathogenic variant AF is 0.00015487835

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 23 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006103.4	RefSeq	NP_006094.3	3	MANE Select
ENST00000372676.8	Ensembl	ENSP00000361761.3	3	MANE Select
ENST00000217425.10	Ensembl	ENSP00000217425.5	3	Standard
ENST00000217425.9	Ensembl	ENSP00000217425.5	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

proteolysis
spermatogenesis
negative regulation of endopeptidase activity

Molecular Function

endopeptidase inhibitor activity
serine-type endopeptidase inhibitor activity
cysteine-type endopeptidase inhibitor activity
aspartic-type endopeptidase inhibitor activity

Cellular Component

extracellular space
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000372676
Coding exons: 3
Length: 11827
Individuals with no LoFs: 103484
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 103485
p: 0.00000483

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0559	69	70.3	0.981	0.00000346	800
Missense (PolyPhen)		20	24.233	0.82533		295
Synonymous	0.286	27	29.0	0.932	0.00000136	240
Loss of Function	2.12	0	5.23	0.00	2.24e-7	60

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000011	0.000011	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Broad range protease inhibitor. {ECO:0000269|PubMed:23139753}.;

Recessive Scores

pRec: 0.176

Intolerance Scores

LoFtool: 0.397
RVIS EVS: -0.08
RVIS percentile EVS: 47.79

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.801

Gene Damage Prediction

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