PRICKLE2

prickle planar cell polarity protein 2, the group of Prickle planar cell polarity proteins|LIM domain containing

Basic information

Region (hg38): 3:64092235-64445476

Links

ENSG00000163637 ∙ NCBI:166336 ∙ OMIM:608501 ∙ HGNC:20340 ∙ Uniprot:Q7Z3G6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• complex neurodevelopmental disorder (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Epilepsy, progessive myoclonic 5	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	632821; 21276947
As with other forms of epilepsy, optimal seizure control is advantageous, and genetic diagnosis may aid with medication selection

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PRICKLE2 gene.

• Progressive myoclonic epilepsy type 5 (367 variants)
• Progressive myoclonic epilepsy (158 variants)
• not provided (42 variants)
• Inborn genetic diseases (31 variants)
• not specified (17 variants)
• See cases (4 variants)
• myoclonic epilepsy (2 variants)
• Myoclonic epilepsy, progressive, X-linked (1 variants)
• PRICKLE2-associated epilepsy syndrome (1 variants)
• - (1 variants)
• Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis (1 variants)
• Childhood epilepsy with centrotemporal spikes (1 variants)
• Autosomal dominant non-syndromic intellectual disability (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PRICKLE2 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			6	110	8	124
missense		2	231	1		234
nonsense	1		1			2
start loss						0
frameshift	1	1				2
inframe indel			4			4
splice donor/acceptor (+/-2bp)						0
splice region			4	6	2	12
non coding			94	22	22	138
Total	2	3	336	133	30

Variants in PRICKLE2

This is a list of pathogenic ClinVar variants found in the PRICKLE2 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-64093959-A-G		Progressive myoclonic epilepsy	Uncertain significance (Jan 12, 2018)
3-64094057-G-A		Progressive myoclonic epilepsy	Uncertain significance (Jan 12, 2018)
3-64094174-G-A		Progressive myoclonic epilepsy	Uncertain significance (Jan 12, 2018)
3-64094189-T-TA		Progressive myoclonic epilepsy	Uncertain significance (Jun 14, 2016)
3-64094254-C-T		Progressive myoclonic epilepsy	Benign (Jan 12, 2018)
3-64094264-A-G		Progressive myoclonic epilepsy	Uncertain significance (Jan 13, 2018)
3-64094282-T-C		Progressive myoclonic epilepsy	Uncertain significance (Jan 13, 2018)
3-64094318-C-T		Progressive myoclonic epilepsy	Benign (Jan 13, 2018)
3-64094456-A-T		Progressive myoclonic epilepsy	Uncertain significance (Jan 13, 2018)
3-64094520-A-G		Progressive myoclonic epilepsy	Uncertain significance (Jan 13, 2018)
3-64094579-C-A		Progressive myoclonic epilepsy	Uncertain significance (Jan 12, 2018)
3-64094596-T-C		Progressive myoclonic epilepsy	Uncertain significance (Jan 13, 2018)
3-64094697-G-C		Progressive myoclonic epilepsy	Likely benign (Jan 12, 2018)
3-64094721-T-A		Progressive myoclonic epilepsy	Uncertain significance (Jan 13, 2018)
3-64094794-A-G		Progressive myoclonic epilepsy	Uncertain significance (Jan 12, 2018)
3-64094813-G-A		Progressive myoclonic epilepsy	Benign (Jan 13, 2018)
3-64094855-A-C		Progressive myoclonic epilepsy	Uncertain significance (Jan 13, 2018)
3-64094869-A-G		Progressive myoclonic epilepsy	Uncertain significance (Jan 13, 2018)
3-64094942-G-C		Progressive myoclonic epilepsy	Uncertain significance (Jan 12, 2018)
3-64094980-T-C		Progressive myoclonic epilepsy	Uncertain significance (Jan 13, 2018)
3-64094994-C-T		Progressive myoclonic epilepsy	Likely benign (Jan 12, 2018)
3-64095187-A-G		Progressive myoclonic epilepsy	Uncertain significance (Jan 13, 2018)
3-64095189-G-T		Progressive myoclonic epilepsy	Uncertain significance (Jan 12, 2018)
3-64095199-G-T		Progressive myoclonic epilepsy	Likely benign (Jan 13, 2018)
3-64095221-A-G		Progressive myoclonic epilepsy	Uncertain significance (Jan 15, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PRICKLE2	protein_coding	protein_coding	ENST00000295902	7	351610

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.995	0.00456	125742	0	6	125748	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.72	396	505	0.784	0.0000332	5585
Missense in Polyphen		60	129.96	0.46168		1440
Synonymous	-0.383	209	202	1.03	0.0000134	1614
Loss of Function	4.96	5	38.0	0.132	0.00000245	399

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000119	0.000119
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.00000880	0.00000879
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Pathway: Wnt signaling pathway - Homo sapiens (human);Wnt Signaling Pathway (Consensus)

Recessive Scores

• pRec: 0.135

Intolerance Scores

• loftool: 0.0756
• rvis_EVS: -1.11
• rvis_percentile_EVS: 6.78

Haploinsufficiency Scores

• pHI: 0.197
• hipred: Y
• hipred_score: 0.853
• ghis: 0.606

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.578

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Prickle2
• 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: prickle2b
• Affected structure: retinal inner plexiform layer
• Phenotype tag: abnormal
• Phenotype quality: disorganized

Gene ontology

• Biological process: Wnt signaling pathway, planar cell polarity pathway
• Cellular component: cytoplasm;nuclear membrane
• Molecular function: zinc ion binding