POLE2

DNA polymerase epsilon 2, accessory subunit, the group of DNA polymerases

Basic information

Region (hg38): 14:49643555-49688422

Links

ENSG00000100479 ∙ NCBI:5427 ∙ OMIM:602670 ∙ HGNC:9178 ∙ Uniprot:P56282 ∙ 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 POLE2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the POLE2 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			4	38	7	49
missense			141	2	5	148
nonsense			5			5
start loss						0
frameshift			12			12
inframe indel						0
splice donor/acceptor (+/-2bp)			3			3
splice region			11	23	2	36
non coding			4	59	7	70
Total	0	0	169	99	19

Variants in POLE2

This is a list of pathogenic ClinVar variants found in the POLE2 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-49643647-G-A		POLE2-related disorder	Benign (Sep 26, 2019)
14-49643672-TG-T			Uncertain significance (Jun 16, 2022)
14-49643674-A-T			Likely benign (Jun 16, 2022)
14-49643675-A-T			Uncertain significance (Jun 16, 2022)
14-49643680-G-GA			Benign (Nov 30, 2024)
14-49643690-T-A			Likely benign (Nov 06, 2024)
14-49647273-G-A			Likely benign (Dec 15, 2022)
14-49647273-G-C			Likely benign (Dec 09, 2023)
14-49647279-G-A			Likely benign (Aug 02, 2023)
14-49647283-A-G			Likely benign (Jun 13, 2024)
14-49647295-A-G			Likely benign (Nov 29, 2024)
14-49647302-A-G			Likely benign (Oct 30, 2024)
14-49647305-G-A			Uncertain significance (Mar 15, 2024)
14-49647307-C-G			Uncertain significance (Oct 26, 2023)
14-49647316-A-T			Likely benign (Mar 24, 2022)
14-49647318-G-A		not specified	Uncertain significance (Aug 15, 2024)
14-49647325-A-C			Benign (Aug 13, 2024)
14-49647327-CTT-C			Uncertain significance (Oct 28, 2024)
14-49647339-A-G			Uncertain significance (Sep 03, 2024)
14-49647340-TC-T			Uncertain significance (Jan 11, 2024)
14-49647350-G-A			Uncertain significance (Oct 09, 2024)
14-49647356-G-C		not specified	Uncertain significance (Aug 04, 2023)
14-49647358-G-A			Likely benign (May 22, 2024)
14-49647359-C-T			Uncertain significance (Mar 19, 2022)
14-49647363-T-C			Uncertain significance (Mar 26, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
POLE2	protein_coding	protein_coding	ENST00000216367	19	44868

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.85e-7	0.996	125678	0	66	125744	0.000262

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.791	232	268	0.864	0.0000136	3432
Missense in Polyphen		56	76.44	0.7326		1017
Synonymous	0.0667	89	89.8	0.991	0.00000446	957
Loss of Function	2.60	16	31.8	0.503	0.00000163	408

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000412	0.000396
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000170	0.000163
Finnish	0.000185	0.000185
European (Non-Finnish)	0.000421	0.000413
Middle Eastern	0.000170	0.000163
South Asian	0.0000691	0.0000653
Other	0.000165	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Participates in DNA repair and in chromosomal DNA replication.
• Pathway: Nucleotide excision repair - Homo sapiens (human);Pyrimidine metabolism - Homo sapiens (human);Base excision repair - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);DNA replication - Homo sapiens (human);Purine metabolism - Homo sapiens (human);Retinoblastoma (RB) in Cancer;Pyrimidine metabolism;G1 to S cell cycle control;DNA Replication;HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA);DNA Repair;DNA Double-Strand Break Repair;Homology Directed Repair;Purine metabolism;Activation of the pre-replicative complex;Mitotic G1-G1/S phases;DNA replication initiation;DNA Replication;Pyrimidine metabolism;Synthesis of DNA;S Phase;PCNA-Dependent Long Patch Base Excision Repair;Resolution of AP sites via the multiple-nucleotide patch replacement pathway;Resolution of Abasic Sites (AP sites);Base Excision Repair;Telomere C-strand synthesis initiation;Telomere C-strand (Lagging Strand) Synthesis;Extension of Telomeres;Telomere Maintenance;Chromosome Maintenance;G1/S Transition;Recognition of DNA damage by PCNA-containing replication complex;DNA Replication Pre-Initiation;M/G1 Transition;Termination of translesion DNA synthesis;Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template;DNA Damage Bypass;Cell Cycle;Dual Incision in GG-NER;Gap-filling DNA repair synthesis and ligation in GG-NER;Global Genome Nucleotide Excision Repair (GG-NER);Cell Cycle, Mitotic;Dual incision in TC-NER;Gap-filling DNA repair synthesis and ligation in TC-NER;Transcription-Coupled Nucleotide Excision Repair (TC-NER);Nucleotide Excision Repair;HDR through Homologous Recombination (HRR) (Consensus)

Recessive Scores

• pRec: 0.0896

Intolerance Scores

• loftool: 0.830
• rvis_EVS: 0.15
• rvis_percentile_EVS: 64.61

Haploinsufficiency Scores

• pHI: 0.962
• hipred: Y
• hipred_score: 0.590
• ghis: 0.620

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.703

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pole2

Zebrafish Information Network

• Gene name: pole2
• Affected structure: trunk
• Phenotype tag: abnormal
• Phenotype quality: necrotic

Gene ontology

• Biological process: G1/S transition of mitotic cell cycle;DNA replication;DNA-dependent DNA replication;DNA repair;error-prone translesion synthesis
• Cellular component: nucleoplasm;epsilon DNA polymerase complex;nuclear body;intracellular membrane-bounded organelle
• Molecular function: DNA binding;DNA-directed DNA polymerase activity;protein binding