DNA2
Basic information
Region (hg38): 10:68414064-68472121
Previous symbols: [ "DNA2L" ]
Links
Phenotypes
GenCC
Source:
- Seckel syndrome 8 (Limited), mode of inheritance: AR
- Seckel syndrome 8 (Moderate), mode of inheritance: AR
- mitochondrial DNA deletion syndrome with progressive myopathy (Moderate), mode of inheritance: AD
- mitochondrial DNA deletion syndrome with progressive myopathy (Supportive), mode of inheritance: AD
- mitochondrial DNA deletion syndrome with progressive myopathy (Strong), mode of inheritance: AD
- Seckel syndrome 8 (Strong), mode of inheritance: AR
Clinical Genomic Database
Source:
Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
---|---|---|---|---|---|
Progressive external ophthalmoplegia with mitochondrial deletions, autosomal dominant, 6; Seckel syndrome 8; Rothmund-Thomson syndrome, type 4 | AD/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 | Biochemical; Craniofacial; Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic | 23352259; 24389050; 37055165 |
ClinVar
This is a list of variants' phenotypes submitted to
- ROTHMUND-THOMSON SYNDROME, TYPE 4 (4 variants)
- Rothmund-Thomson syndrome (4 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the DNA2 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 | 107 | 119 | ||||
missense | 322 | 13 | 342 | |||
nonsense | 11 | 11 | ||||
start loss | 0 | |||||
frameshift | 22 | 28 | ||||
inframe indel | 1 | |||||
splice donor/acceptor (+/-2bp) | 11 | 13 | ||||
splice region | 1 | 12 | 20 | 3 | 36 | |
non coding | 114 | 63 | 184 | |||
Total | 1 | 9 | 378 | 235 | 75 |
Variants in DNA2
This is a list of pathogenic ClinVar variants found in the DNA2 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
Position | Type | Phenotype | Significance | ClinVar |
---|---|---|---|---|
10-68414836-TA-T | Likely benign (Jul 31, 2018) | |||
10-68414950-T-A | Benign (Jun 23, 2018) | |||
10-68415060-CA-C | Uncertain significance (Mar 04, 2022) | |||
10-68415065-T-C | Uncertain significance (Oct 21, 2021) | |||
10-68415085-T-C | Uncertain significance (Sep 23, 2023) | |||
10-68415100-T-C | Uncertain significance (Feb 14, 2022) | |||
10-68415105-G-T | Likely benign (Nov 05, 2023) | |||
10-68415126-G-A | Likely benign (Dec 03, 2022) | |||
10-68415128-A-G | Benign (Jun 26, 2018) | |||
10-68415205-CA-C | Benign (Aug 20, 2019) | |||
10-68415275-CT-C | Benign (Aug 12, 2019) | |||
10-68416402-G-A | Benign (Jun 14, 2018) | |||
10-68416697-G-T | Likely benign (Jun 03, 2023) | |||
10-68416697-G-GA | Benign (Jan 15, 2022) | |||
10-68416702-AG-A | Seckel syndrome 8 • Ateleiotic dwarfism | Pathogenic/Likely pathogenic (Feb 01, 2014) | ||
10-68416712-T-C | Likely benign (May 11, 2022) | |||
10-68416724-T-C | Likely benign (Nov 01, 2022) | |||
10-68416727-A-G | Likely benign (Nov 01, 2022) | |||
10-68416732-T-C | Uncertain significance (Jun 22, 2022) | |||
10-68416736-C-G | Likely benign (Oct 01, 2022) | |||
10-68416736-C-T | not specified | Likely benign (May 19, 2017) | ||
10-68416739-C-A | Uncertain significance (Nov 07, 2019) | |||
10-68416749-G-A | Uncertain significance (Nov 28, 2023) | |||
10-68416753-G-A | Uncertain significance (Jul 06, 2022) | |||
10-68416755-T-G | Uncertain significance (Feb 28, 2023) |
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
DNA2 | protein_coding | protein_coding | ENST00000399180 | 21 | 58059 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
1.27e-18 | 0.652 | 124216 | 4 | 433 | 124653 | 0.00175 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | 0.736 | 524 | 574 | 0.914 | 0.0000285 | 7492 |
Missense in Polyphen | 139 | 178.81 | 0.77736 | 2334 | ||
Synonymous | 0.466 | 193 | 201 | 0.958 | 0.00000981 | 2124 |
Loss of Function | 1.98 | 36 | 51.3 | 0.702 | 0.00000254 | 688 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.000862 | 0.000861 |
Ashkenazi Jewish | 0.000123 | 0.0000993 |
East Asian | 0.000470 | 0.000445 |
Finnish | 0.00122 | 0.00111 |
European (Non-Finnish) | 0.000356 | 0.000345 |
Middle Eastern | 0.000470 | 0.000445 |
South Asian | 0.0119 | 0.0111 |
Other | 0.000886 | 0.000826 |
dbNSFP
Source:
- Function
- FUNCTION: Key enzyme involved in DNA replication and DNA repair in nucleus and mitochondrion. Involved in Okazaki fragments processing by cleaving long flaps that escape FEN1: flaps that are longer than 27 nucleotides are coated by replication protein A complex (RPA), leading to recruit DNA2 which cleaves the flap until it is too short to bind RPA and becomes a substrate for FEN1. Also involved in 5'-end resection of DNA during double- strand break (DSB) repair: recruited by BLM and mediates the cleavage of 5'-ssDNA, while the 3'-ssDNA cleavage is prevented by the presence of RPA. Also involved in DNA replication checkpoint independently of Okazaki fragments processing. Possesses different enzymatic activities, such as single-stranded DNA (ssDNA)- dependent ATPase, 5'-3' helicase and endonuclease activities. While the ATPase and endonuclease activities are well-defined and play a key role in Okazaki fragments processing and DSB repair, the 5'-3' DNA helicase activity is subject to debate. According to various reports, the helicase activity is weak and its function remains largely unclear. Helicase activity may promote the motion of DNA2 on the flap, helping the nuclease function. {ECO:0000269|PubMed:16595799, ECO:0000269|PubMed:16595800, ECO:0000269|PubMed:18995831, ECO:0000269|PubMed:19487465, ECO:0000269|PubMed:21325134, ECO:0000269|PubMed:21572043, ECO:0000269|PubMed:22570407, ECO:0000269|PubMed:22570476}.;
- Disease
- DISEASE: Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 6 (PEOA6) [MIM:615156]: A disorder characterized by muscle weakness, mainly affecting the lower limbs, external ophthalmoplegia, exercise intolerance, and mitochondrial DNA deletions on muscle biopsy. Symptoms may appear in childhood or adulthood and show slow progression. {ECO:0000269|PubMed:23352259}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Seckel syndrome 8 (SCKL8) [MIM:615807]: A rare autosomal recessive disorder characterized by proportionate dwarfism of prenatal onset associated with low birth weight, growth retardation, severe microcephaly with a bird-headed like appearance, and mental retardation. {ECO:0000269|PubMed:24389050}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- DNA replication - Homo sapiens (human);HDR through Single Strand Annealing (SSA);HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA);DNA Repair;Gene expression (Transcription);DNA Double-Strand Break Repair;Generic Transcription Pathway;Homology Directed Repair;RNA Polymerase II Transcription;G2/M DNA damage checkpoint;G2/M Checkpoints;Cell Cycle Checkpoints;DNA Replication;Removal of the Flap Intermediate;Processive synthesis on the lagging strand;Lagging Strand Synthesis;DNA strand elongation;Synthesis of DNA;S Phase;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;Regulation of TP53 Activity through Phosphorylation;Regulation of TP53 Activity;Transcriptional Regulation by TP53;Cell Cycle;Cell Cycle, Mitotic;Processing of DNA double-strand break ends;Presynaptic phase of homologous DNA pairing and strand exchange;Homologous DNA Pairing and Strand Exchange;Resolution of D-loop Structures through Holliday Junction Intermediates;Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA);Resolution of D-Loop Structures;HDR through Homologous Recombination (HRR)
(Consensus)
Haploinsufficiency Scores
- pHI
- 0.622
- hipred
- Y
- hipred_score
- 0.704
- ghis
- 0.606
Essentials
- essential_gene_CRISPR
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.381
Gene Damage Prediction
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | Medium | Medium | Medium |
Primary Immunodeficiency | Medium | Medium | Medium |
Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Dna2
- 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); neoplasm; cellular phenotype;
Gene ontology
- Biological process
- DNA replication checkpoint;telomere maintenance;DNA double-strand break processing;DNA replication;mitochondrial DNA replication;base-excision repair;telomere maintenance via semi-conservative replication;DNA duplex unwinding;DNA replication, Okazaki fragment processing;DNA replication, removal of RNA primer;mitochondrial DNA repair;G-quadruplex DNA unwinding;positive regulation of DNA replication;replication fork reversal;nucleic acid phosphodiester bond hydrolysis;t-circle formation;mitotic telomere maintenance via semi-conservative replication
- Cellular component
- nuclear chromosome, telomeric region;nucleus;nucleoplasm;cytoplasm;mitochondrion;gamma DNA polymerase complex;mitochondrial nucleoid
- Molecular function
- DNA binding;DNA helicase activity;RNA binding;helicase activity;nuclease activity;protein binding;ATP binding;ATPase activity;site-specific endodeoxyribonuclease activity, specific for altered base;5'-flap endonuclease activity;5'-3' DNA helicase activity;single-stranded DNA-dependent ATPase activity;metal ion binding;4 iron, 4 sulfur cluster binding