POLD2

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

Basic information

Region (hg38): 7:44114631-44124358

Links

ENSG00000106628 ∙ NCBI:5425 ∙ OMIM:600815 ∙ HGNC:9176 ∙ Uniprot:P49005 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• non-severe combined immunodeficiency due to polymerase delta deficiency (Limited), mode of inheritance: AR

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the POLD2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the POLD2 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			2	58	8	68
missense			117	1	1	119
nonsense			2			2
start loss						0
frameshift			3			3
inframe indel			2			2
splice donor/acceptor (+/-2bp)			1			1
splice region			4	9	3	16
non coding			13	35	5	53
Total	0	0	140	94	14

Variants in POLD2

This is a list of pathogenic ClinVar variants found in the POLD2 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-44114793-C-T			Uncertain significance (Apr 06, 2022)
7-44114794-C-CA			Uncertain significance (Apr 04, 2022)
7-44114797-C-A			Likely benign (Feb 11, 2022)
7-44114798-C-G			Uncertain significance (Nov 24, 2023)
7-44114798-C-T			Uncertain significance (Aug 10, 2023)
7-44114801-A-AG			Uncertain significance (Dec 28, 2022)
7-44114812-G-C			Uncertain significance (Nov 07, 2022)
7-44114813-T-TCATC			Uncertain significance (Jun 08, 2022)
7-44114817-C-G			Uncertain significance (Aug 24, 2022)
7-44114817-C-T		not specified	Uncertain significance (May 03, 2024)
7-44114818-G-A			Likely benign (Oct 15, 2024)
7-44114821-C-G			Uncertain significance (May 30, 2024)
7-44114821-C-T			Likely benign (Sep 24, 2022)
7-44114826-C-T		not specified	Uncertain significance (Oct 12, 2024)
7-44114829-C-T			Uncertain significance (May 21, 2022)
7-44114830-G-A			Likely benign (Feb 02, 2023)
7-44114836-C-T			Likely benign (Oct 30, 2024)
7-44114837-G-A			Uncertain significance (Aug 12, 2024)
7-44114854-G-A			Benign/Likely benign (Jan 29, 2025)
7-44114867-C-T			Uncertain significance (Sep 21, 2024)
7-44114868-G-A			Uncertain significance (Sep 05, 2024)
7-44114877-C-T		not specified	Uncertain significance (Dec 27, 2023)
7-44114886-C-T		not specified	Uncertain significance (Nov 11, 2024)
7-44114887-G-A			Likely benign (Nov 22, 2024)
7-44114888-G-A			Uncertain significance (Mar 04, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
POLD2	protein_coding	protein_coding	ENST00000406581	10	9672

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000972	0.997	125718	0	29	125747	0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.65	212	291	0.729	0.0000177	3027
Missense in Polyphen		58	88.961	0.65197		945
Synonymous	0.581	118	126	0.934	0.00000806	981
Loss of Function	2.66	9	22.7	0.397	0.00000123	238

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000268	0.000268
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.0000545	0.0000544
Finnish	0.0000928	0.0000924
European (Non-Finnish)	0.000126	0.000123
Middle Eastern	0.0000545	0.0000544
South Asian	0.000131	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: As a component of the trimeric and tetrameric DNA polymerase delta complexes (Pol-delta3 and Pol-delta4, respectively), plays a role in high fidelity genome replication, including in lagging strand synthesis, and repair (PubMed:12403614, PubMed:16510448, PubMed:19074196, PubMed:20334433, PubMed:24035200). Pol-delta3 and Pol-delta4 are characterized by the absence or the presence of POLD4. They exhibit differences in catalytic activity. Most notably, Pol- delta3 shows higher proofreading activity than Pol-delta4 (PubMed:19074196, PubMed:20334433). Although both Pol-delta3 and Pol-delta4 process Okazaki fragments in vitro, Pol-delta3 may also be better suited to fulfill this task, exhibiting near-absence of strand displacement activity compared to Pol-delta4 and stalling on encounter with the 5'-blocking oligonucleotides. Pol-delta3 idling process may avoid the formation of a gap, while maintaining a nick that can be readily ligated (PubMed:24035200). Along with DNA polymerase kappa, DNA polymerase delta carries out approximately half of nucleotide excision repair (NER) synthesis following UV irradiation (PubMed:20227374). Under conditions of DNA replication stress, required for the repair of broken replication forks through break-induced replication (BIR) (PubMed:24310611). Involved in the translesion synthesis (TLS) of templates carrying O6-methylguanine or abasic sites performed by Pol-delta4, independently of DNA polymerase zeta (REV3L) or eta (POLH). Facilitates abasic site bypass by DNA polymerase delta by promoting extension from the nucleotide inserted opposite the lesion. Also involved in TLS as a component of the POLZ complex. Along with POLD3, dramatically increases the efficiency and processivity of DNA synthesis of the minimal DNA polymerase zeta complex, consisting of only REV3L and REV7 (PubMed:24449906). {ECO:0000269|PubMed:12403614, ECO:0000269|PubMed:16510448, ECO:0000269|PubMed:19074196, ECO:0000269|PubMed:20227374, ECO:0000269|PubMed:20334433, ECO:0000269|PubMed:24035200, ECO:0000269|PubMed:24310611, ECO:0000269|PubMed:24449906}.
• Pathway: Nucleotide excision repair - Homo sapiens (human);Pyrimidine metabolism - Homo sapiens (human);Base excision repair - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);Mismatch repair - Homo sapiens (human);DNA replication - Homo sapiens (human);Purine metabolism - Homo sapiens (human);Homologous recombination - Homo sapiens (human);miR-targeted genes in epithelium - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;miR-targeted genes in squamous cell - TarBase;Homologous recombination;Pyrimidine metabolism;DNA Replication;Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta);Mismatch Repair;HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA);DNA Repair;DNA Double-Strand Break Repair;Homology Directed Repair;Polymerase switching on the C-strand of the telomere;Purine metabolism;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;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;Removal of the Flap Intermediate from the C-strand;Processive synthesis on the C-strand of the telomere;Telomere C-strand (Lagging Strand) Synthesis;Extension of Telomeres;Telomere Maintenance;Chromosome Maintenance;Recognition of DNA damage by PCNA-containing replication complex;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;Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha);HDR through Homologous Recombination (HRR) (Consensus)

Recessive Scores

• pRec: 0.224

Intolerance Scores

• loftool: 0.639
• rvis_EVS: -0.91
• rvis_percentile_EVS: 9.9

Haploinsufficiency Scores

• pHI: 0.336
• hipred: N
• hipred_score: 0.426
• ghis: 0.668

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.997

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pold2
• 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)

Gene ontology

• Biological process: telomere maintenance;DNA replication;DNA strand elongation involved in DNA replication;transcription-coupled nucleotide-excision repair;nucleotide-excision repair, DNA incision, 5'-to lesion;nucleotide-excision repair, DNA gap filling;translesion synthesis;telomere maintenance via semi-conservative replication;nucleotide-excision repair, DNA incision;DNA damage response, detection of DNA damage
• Cellular component: nucleus;nucleoplasm;delta DNA polymerase complex
• Molecular function: DNA binding;DNA-directed DNA polymerase activity;protein binding