DVL2

dishevelled segment polarity protein 2, the group of PDZ domain containing|Dishevelled segment polarity proteins

Basic information

Region (hg38): 17:7225342-7234517

Links

ENSG00000004975 ∙ NCBI:1856 ∙ OMIM:602151 ∙ HGNC:3086 ∙ Uniprot:O14641 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DVL2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DVL2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				3	4	7
missense			41	4	2	47
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				3	1	4
non coding				2	3	5
Total	0	0	41	9	9

Variants in DVL2

This is a list of pathogenic ClinVar variants found in the DVL2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-7225357-G-A			Benign (Jul 07, 2018)
17-7225408-C-T			Likely benign (Aug 14, 2018)
17-7225870-T-A		not specified	Uncertain significance (Dec 09, 2023)
17-7225891-T-G		not specified	Uncertain significance (Feb 12, 2024)
17-7225980-G-A		not specified	Uncertain significance (Dec 31, 2023)
17-7226008-G-A		not specified	Uncertain significance (Jun 05, 2024)
17-7226190-C-T		not specified	Uncertain significance (Mar 12, 2024)
17-7226196-C-T		not specified	Uncertain significance (May 05, 2023)
17-7226245-C-A		not specified	Uncertain significance (Aug 30, 2021)
17-7226250-T-C		not specified	Uncertain significance (Feb 12, 2024)
17-7226262-C-G		not specified	Uncertain significance (Feb 07, 2023)
17-7226280-C-G		not specified	Uncertain significance (Feb 07, 2023)
17-7226456-T-C		not specified	Uncertain significance (Mar 19, 2024)
17-7226459-G-A		not specified	Uncertain significance (Feb 26, 2024)
17-7226478-G-A		not specified	Uncertain significance (Dec 27, 2023)
17-7226521-T-C			Benign (Jun 22, 2021)
17-7226525-T-A		not specified	Uncertain significance (Feb 28, 2024)
17-7226579-G-A		DVL2-related disorder	Benign (Nov 08, 2019)
17-7226655-A-G			Benign (Jun 22, 2021)
17-7227219-G-A		not specified	Uncertain significance (Jun 11, 2021)
17-7227237-C-T		not specified	Uncertain significance (Apr 15, 2024)
17-7227509-G-A		not specified	Uncertain significance (Oct 25, 2022)
17-7227512-C-A		not specified	Uncertain significance (Feb 05, 2024)
17-7227512-C-T		not specified	Likely benign (Dec 19, 2022)
17-7227523-C-T		DVL2-related disorder	Benign (Oct 10, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DVL2	protein_coding	protein_coding	ENST00000005340	15	9205

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000136	1.00	125723	0	25	125748	0.0000994

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.322	447	467	0.958	0.0000280	4747
Missense in Polyphen		170	212.54	0.79984		2129
Synonymous	-1.14	209	189	1.11	0.0000121	1541
Loss of Function	3.10	14	33.3	0.420	0.00000184	354

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000248	0.000248
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.0000464	0.0000462
European (Non-Finnish)	0.000104	0.0000967
Middle Eastern	0.000163	0.000163
South Asian	0.0000981	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a role in the signal transduction pathways mediated by multiple Wnt genes. Participates both in canonical and non-canonical Wnt signaling by binding to the cytoplasmic C- terminus of frizzled family members and transducing the Wnt signal to down-stream effectors. Promotes internalization and degradation of frizzled proteins upon Wnt signaling. {ECO:0000250|UniProtKB:Q60838, ECO:0000269|PubMed:19252499}.
• Pathway: Gastric cancer - Homo sapiens (human);mTOR signaling pathway - Homo sapiens (human);Cushing,s syndrome - Homo sapiens (human);Breast cancer - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human);Basal cell carcinoma - Homo sapiens (human);Hepatocellular carcinoma - Homo sapiens (human);Hippo signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Wnt signaling pathway - Homo sapiens (human);Notch signaling pathway - Homo sapiens (human);Melanogenesis - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);WNT-Core;Neural Crest Differentiation;Notch Signaling Pathway;Wnt Signaling Pathway;Regulation of Wnt-B-catenin Signaling by Small Molecule Compounds;ESC Pluripotency Pathways;Wnt Signaling Pathway and Pluripotency;Wnt Signaling in Kidney Disease;Type 2 papillary renal cell carcinoma;Notch Signaling Pathway;Wnt Signaling Pathway;DNA Damage Response (only ATM dependent);Signaling by WNT;Signal Transduction;Vesicle-mediated transport;Membrane Trafficking;RHO GTPases Activate Formins;Disassembly of the destruction complex and recruitment of AXIN to the membrane;RHO GTPase Effectors;Signaling by Rho GTPases;Clathrin-mediated endocytosis;Asymmetric localization of PCP proteins;WNT5A-dependent internalization of FZD4;PCP/CE pathway;Beta-catenin independent WNT signaling;Noncanonical Wnt signaling pathway;Cargo recognition for clathrin-mediated endocytosis;Negative regulation of TCF-dependent signaling by DVL-interacting proteins;Degradation of DVL;Signaling by Hippo;Wnt;Wnt Canonical;WNT mediated activation of DVL;Degradation of beta catenin;TCF dependent signaling in response to WNT;Canonical Wnt signaling pathway;Wnt Mammals (Consensus)

Recessive Scores

• pRec: 0.214

Intolerance Scores

• loftool: 0.650
• rvis_EVS: -1.21
• rvis_percentile_EVS: 5.69

Haploinsufficiency Scores

• pHI: 0.920
• hipred: Y
• hipred_score: 0.765
• ghis: 0.595

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.995

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dvl2
• Phenotype: embryo phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; skeleton phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype; craniofacial phenotype

Zebrafish Information Network

• Gene name: dvl2
• Affected structure: head
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• Biological process: neural tube closure;positive regulation of protein phosphorylation;outflow tract morphogenesis;transcription by RNA polymerase II;segment specification;heart development;convergent extension involved in neural plate elongation;cellular protein localization;hippo signaling;non-canonical Wnt signaling pathway;positive regulation of JUN kinase activity;positive regulation of GTPase activity;canonical Wnt signaling pathway involved in regulation of cell proliferation;positive regulation of transcription, DNA-templated;positive regulation of DNA-binding transcription factor activity;protein complex oligomerization;canonical Wnt signaling pathway;Wnt signaling pathway, planar cell polarity pathway;membrane organization;positive regulation of protein tyrosine kinase activity;negative regulation of canonical Wnt signaling pathway;cochlea morphogenesis;planar cell polarity pathway involved in neural tube closure;positive regulation of neuron projection arborization;beta-catenin destruction complex disassembly
• Cellular component: nucleus;nucleoplasm;cytoplasm;cytosol;aggresome;lateral plasma membrane;nuclear body;cytoplasmic vesicle;apical part of cell;clathrin-coated endocytic vesicle
• Molecular function: frizzled binding;protein binding;protein kinase binding;protein domain specific binding;protein binding, bridging;identical protein binding;protein self-association;Rac GTPase binding