POLA2

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

Basic information

Region (hg38): 11:65261913-65305959

Links

ENSG00000014138 ∙ NCBI:23649 ∙ OMIM:620063 ∙ HGNC:30073 ∙ Uniprot:Q14181 ∙ 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 POLA2 gene.

• Telomere Biology Disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the POLA2 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						0
missense		1	42	1		44
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	1	42	1	0

Variants in POLA2

This is a list of pathogenic ClinVar variants found in the POLA2 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-65262306-C-T		not specified	Uncertain significance (Feb 06, 2023)
11-65262325-G-C		not specified	Uncertain significance (Oct 05, 2022)
11-65262369-A-G		not specified	Uncertain significance (Sep 16, 2021)
11-65266642-C-G		not specified	Uncertain significance (Jan 19, 2024)
11-65266646-C-G		not specified	Uncertain significance (Dec 07, 2023)
11-65266691-C-G		not specified	Uncertain significance (Oct 05, 2023)
11-65267483-A-G		not specified	Uncertain significance (Dec 02, 2022)
11-65267496-C-T		not specified	Uncertain significance (May 29, 2024)
11-65267517-G-T		not specified	Uncertain significance (May 07, 2024)
11-65267559-T-C		Telomere Biology Disorder	Likely pathogenic (Jan 09, 2024)
11-65268676-G-A		not specified	Uncertain significance (Oct 12, 2021)
11-65275952-A-G		not specified	Likely benign (Sep 27, 2024)
11-65275965-A-G		not specified	Uncertain significance (Sep 30, 2021)
11-65278768-G-A		not specified	Uncertain significance (Nov 09, 2024)
11-65279552-A-G		not specified	Uncertain significance (Aug 05, 2024)
11-65281010-G-A		not specified	Uncertain significance (Nov 03, 2023)
11-65281017-T-C		not specified	Uncertain significance (Dec 20, 2023)
11-65281064-G-A		not specified	Uncertain significance (May 11, 2022)
11-65281086-C-T		not specified	Uncertain significance (Jan 10, 2023)
11-65281115-G-A		not specified	Uncertain significance (Jun 26, 2024)
11-65281676-A-T		not specified	Uncertain significance (Oct 09, 2024)
11-65282482-G-A		not specified	Uncertain significance (Nov 12, 2024)
11-65287760-A-G		not specified	Uncertain significance (Feb 22, 2023)
11-65289065-G-C		not specified	Uncertain significance (May 05, 2023)
11-65289068-G-A		not specified	Uncertain significance (Feb 22, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
POLA2	protein_coding	protein_coding	ENST00000265465	18	43828

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.73e-7	1.00	125702	0	46	125748	0.000183

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.06	278	332	0.837	0.0000176	3857
Missense in Polyphen		78	100.24	0.77812		1138
Synonymous	0.189	137	140	0.980	0.00000857	1206
Loss of Function	3.29	17	39.2	0.434	0.00000225	421

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000269	0.000269
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000463	0.0000462
European (Non-Finnish)	0.000240	0.000237
Middle Eastern	0.0000544	0.0000544
South Asian	0.000264	0.000261
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May play an essential role at the early stage of chromosomal DNA replication by coupling the polymerase alpha/primase complex to the cellular replication machinery. {ECO:0000250}.
• Pathway: Pyrimidine metabolism - Homo sapiens (human);DNA replication - Homo sapiens (human);Purine metabolism - Homo sapiens (human);miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;Pyrimidine metabolism;G1 to S cell cycle control;DNA Replication;Inhibition of replication initiation of damaged DNA by RB1/E2F1;Polymerase switching on the C-strand of the telomere;Purine metabolism;Activation of the pre-replicative complex;E2F mediated regulation of DNA replication;Mitotic G1-G1/S phases;DNA replication initiation;DNA Replication;Pyrimidine metabolism;Polymerase switching;Leading Strand Synthesis;Removal of the Flap Intermediate;Processive synthesis on the lagging strand;Lagging Strand Synthesis;DNA strand elongation;Synthesis of DNA;S Phase;Telomere C-strand synthesis initiation;Telomere C-strand (Lagging Strand) Synthesis;Extension of Telomeres;Telomere Maintenance;Chromosome Maintenance;G1/S Transition;DNA Replication Pre-Initiation;M/G1 Transition;Cell Cycle;Cell Cycle, Mitotic (Consensus)

Recessive Scores

• pRec: 0.269

Intolerance Scores

• loftool: 0.705
• rvis_EVS: -0.78
• rvis_percentile_EVS: 12.97

Haploinsufficiency Scores

• pHI: 0.517
• hipred: Y
• hipred_score: 0.634
• ghis: 0.685

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.999

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pola2
• Phenotype: 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); homeostasis/metabolism phenotype

Gene ontology

• Biological process: G1/S transition of mitotic cell cycle;DNA replication;DNA replication initiation;telomere maintenance via semi-conservative replication;DNA biosynthetic process
• Cellular component: nucleoplasm;alpha DNA polymerase:primase complex;cytosol
• Molecular function: molecular_function;DNA binding;DNA-directed DNA polymerase activity;protein heterodimerization activity