PCNT

pericentrin

Basic information

Region (hg38): 21:46324123-46445769

Previous symbols: [ "PCNT2" ]

Links

ENSG00000160299 ∙ NCBI:5116 ∙ OMIM:605925 ∙ HGNC:16068 ∙ Uniprot:O95613 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• microcephalic osteodysplastic primordial dwarfism type II (Definitive), mode of inheritance: AR
• Moyamoya disease (Moderate), mode of inheritance: AR
• microcephalic osteodysplastic primordial dwarfism type II (Definitive), mode of inheritance: AR
• microcephalic osteodysplastic primordial dwarfism type II (Strong), mode of inheritance: AR
• microcephalic osteodysplastic primordial dwarfism type II (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Microcephalic osteodysplastic primordial dwarfism, type II	AR	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	Craniofacial; Musculoskeletal; Neurologic	7201238; 9800906; 9800908; 12400072; 12210304; 15368497; 15372530; 18157127; 18174396; 20358609; 19643772; 21567919
Individuals may have cerebral neurovascular anomalies

ClinVar

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

• not provided (149 variants)
• Microcephalic osteodysplastic primordial dwarfism type II (39 variants)
• Inborn genetic diseases (4 variants)
• PCNT-related disorder (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PCNT 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			15	989	31	1035
missense			772	67	36	875
nonsense	78	14	2			94
start loss						0
frameshift	91	17	7			115
inframe indel			26	5		31
splice donor/acceptor (+/-2bp)	7	39	1			47
splice region			28	125	13	166
non coding		1	21	485	162	669
Total	176	71	844	1546	229

Highest pathogenic variant AF is 0.0000460

Variants in PCNT

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

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

Position	Type	Phenotype	Significance	ClinVar
21-46324123-CG-C		Microcephalic osteodysplastic primordial dwarfism	Benign (Jun 14, 2016)
21-46324123-C-CG		Microcephalic osteodysplastic primordial dwarfism	Uncertain significance (Jun 14, 2016)
21-46324154-G-A		Microcephalic osteodysplastic primordial dwarfism	Uncertain significance (Jun 14, 2016)
21-46324194-T-A		Microcephalic osteodysplastic primordial dwarfism type II	Uncertain significance (Jan 12, 2018)
21-46324196-A-G		Microcephalic osteodysplastic primordial dwarfism type II	Uncertain significance (Jan 13, 2018)
21-46324204-G-C		Microcephalic osteodysplastic primordial dwarfism type II	Likely benign (Jan 13, 2018)
21-46324213-G-T		not specified • Microcephalic osteodysplastic primordial dwarfism type II	Benign (Jan 12, 2018)
21-46324214-C-G			Likely benign (Apr 19, 2018)
21-46324223-A-T		PCNT-related disorder	Likely benign (Apr 07, 2021)
21-46324235-G-A		Inborn genetic diseases	Uncertain significance (Nov 18, 2023)
21-46324235-G-C		Microcephalic osteodysplastic primordial dwarfism type II	Likely benign (Apr 28, 2021)
21-46324244-G-C		not specified • Microcephalic osteodysplastic primordial dwarfism type II	Uncertain significance (Jul 01, 2020)
21-46324249-G-A			Likely benign (Feb 22, 2023)
21-46324250-CGGCGCAGAAA-C			Pathogenic (Mar 02, 2023)
21-46324252-G-A			Likely benign (May 19, 2023)
21-46324252-G-C		PCNT-related disorder	Conflicting classifications of pathogenicity (Dec 12, 2023)
21-46324255-C-T			Likely benign (Nov 13, 2023)
21-46324257-G-C		PCNT-related disorder	Uncertain significance (Jan 11, 2024)
21-46324261-G-A			Likely benign (Jan 31, 2024)
21-46324264-G-A			Likely benign (Sep 08, 2023)
21-46324273-G-A			Likely benign (Jan 31, 2024)
21-46324273-G-C			Likely benign (Jan 02, 2024)
21-46324274-A-C			Likely benign (Apr 28, 2023)
21-46324276-G-A			Likely benign (Feb 01, 2024)
21-46324277-A-G		not specified	Likely benign (Jun 09, 2017)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PCNT	protein_coding	protein_coding	ENST00000359568	47	121647

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.02e-58	0.476	125383	1	364	125748	0.00145

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.73	2093	1.88e+3	1.11	0.000129	21658
Missense in Polyphen		172	179.54	0.95802		2051
Synonymous	-4.52	975	811	1.20	0.0000589	6485
Loss of Function	3.53	117	166	0.705	0.00000901	1901

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00278	0.00278
Ashkenazi Jewish	0.00695	0.00368
East Asian	0.000544	0.000544
Finnish	0.000204	0.000185
European (Non-Finnish)	0.00138	0.00128
Middle Eastern	0.000544	0.000544
South Asian	0.00282	0.00281
Other	0.00196	0.00179

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Integral component of the filamentous matrix of the centrosome involved in the initial establishment of organized microtubule arrays in both mitosis and meiosis. Plays a role, together with DISC1, in the microtubule network formation. Is an integral component of the pericentriolar material (PCM). May play an important role in preventing premature centrosome splitting during interphase by inhibiting NEK2 kinase activity at the centrosome. {ECO:0000269|PubMed:10823944, ECO:0000269|PubMed:11171385, ECO:0000269|PubMed:18955030, ECO:0000269|PubMed:20599736}.
• Disease: DISEASE: Microcephalic osteodysplastic primordial dwarfism 2 (MOPD2) [MIM:210720]: Adults with this rare inherited condition have an average height of 100 centimeters and a brain size comparable to that of a 3-month-old baby, but are of near-normal intelligence. {ECO:0000269|PubMed:18157127, ECO:0000269|PubMed:18174396}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Olfactory bulb development and olfactory learning;Regulation of PLK1 Activity at G2/M Transition;Recruitment of mitotic centrosome proteins and complexes;Loss of Nlp from mitotic centrosomes;Loss of proteins required for interphase microtubule organization from the centrosome;Centrosome maturation;AURKA Activation by TPX2;G2/M Transition;Mitotic G2-G2/M phases;Recruitment of NuMA to mitotic centrosomes;Mitotic Prometaphase;M Phase;Cell Cycle;Cell Cycle, Mitotic;Anchoring of the basal body to the plasma membrane;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.214

Intolerance Scores

• loftool: 0.898
• rvis_EVS: 3.57
• rvis_percentile_EVS: 99.52

Haploinsufficiency Scores

• pHI: 0.122
• hipred: Y
• hipred_score: 0.519
• ghis: 0.463

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.898

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pcnt
• Phenotype: growth/size/body region phenotype; craniofacial phenotype; homeostasis/metabolism phenotype; cellular phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); vision/eye phenotype; digestive/alimentary phenotype; limbs/digits/tail 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); renal/urinary system phenotype; skeleton phenotype

Gene ontology

• Biological process: G2/M transition of mitotic cell cycle;microtubule cytoskeleton organization;mitotic spindle organization;signal transduction;regulation of G2/M transition of mitotic cell cycle;cilium assembly;positive regulation of intracellular protein transport;ciliary basal body-plasma membrane docking
• Cellular component: centrosome;centriole;microtubule organizing center;cytosol;microtubule;membrane;centriolar satellite
• Molecular function: protein binding;calmodulin binding;protein-containing complex scaffold activity