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

telomere syndrome (Limited), mode of inheritance: AR

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the POLA2 gene.

not_specified (70 variants)
Telomere_Biology_Disorder (3 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. These statistics are base on transcript: NM_000002689.4. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar			2
missense		2 clinvar	70 clinvar	1 clinvar		73
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	2	76	1	0

Highest pathogenic variant AF is 0.00003181094

Loading clinvar variants...

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