DNASE2

deoxyribonuclease 2, lysosomal

Basic information

Region (hg38): 19:12875209-12881595

Previous symbols: [ "DNL", "DNL2" ]

Links

ENSG00000105612 ∙ NCBI:1777 ∙ OMIM:126350 ∙ HGNC:2960 ∙ Uniprot:O00115 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autoinflammatory-pancytopenia syndrome due to DNASE2 deficiency (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Autoinflammatory-pancytopenia syndrome	AR	Allergy/Immunology/Infectious	The condition can involve autoinflammatory sequelae, and medical management (eg , via JAK inhibition) has been described as beneficial	Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Neurologic; Renal	29259162; 31775019

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DNASE2 gene.

• not_provided (155 variants)
• not_specified (28 variants)
• Autoinflammatory-pancytopenia_syndrome_due_to_DNASE2_deficiency (5 variants)
• DNASE2-related_disorder (5 variants)
• Systemic_lupus_erythematosus (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DNASE2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000001375.3. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	46	1	48
missense	3		78	5	3	89
nonsense			4			4
start loss						0
frameshift			1			1
splice donor/acceptor (+/-2bp)			1			1
Total	3	0	85	51	4

Highest pathogenic variant AF is 0.0000027361802

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DNASE2	protein_coding	protein_coding	ENST00000222219	6	6258

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000452	0.968	125732	0	16	125748	0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.644	170	195	0.870	0.0000104	2336
Missense in Polyphen		67	81.263	0.82448		970
Synonymous	0.0233	88	88.3	0.997	0.00000539	720
Loss of Function	1.91	8	16.3	0.490	7.28e-7	164

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000185	0.000185
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000618	0.0000615
Middle Eastern	0.000109	0.000109
South Asian	0.0000980	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Hydrolyzes DNA under acidic conditions with a preference for double-stranded DNA. Plays a major role in the degradation of nuclear DNA in cellular apoptosis during development. Necessary for proper fetal development and for definitive erythropoiesis in fetal liver, where it degrades nuclear DNA expelled from erythroid precursor cells.
• Pathway: Lysosome - Homo sapiens (human);Lysosome Vesicle Biogenesis;Clathrin derived vesicle budding;trans-Golgi Network Vesicle Budding;Vesicle-mediated transport;Membrane Trafficking (Consensus)

Recessive Scores

• pRec: 0.131

Intolerance Scores

• loftool: 0.497
• rvis_EVS: 0.39
• rvis_percentile_EVS: 76.05

Haploinsufficiency Scores

• pHI: 0.0752
• hipred: N
• hipred_score: 0.247
• ghis: 0.394

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.827

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dnase2a
• Phenotype: growth/size/body region phenotype; endocrine/exocrine gland phenotype; muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype; skeleton 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); hematopoietic system phenotype; immune system phenotype

Gene ontology

• Biological process: DNA metabolic process;apoptotic DNA fragmentation;erythrocyte differentiation;regulation of immune response
• Cellular component: lysosome;extracellular exosome
• Molecular function: DNA binding;deoxyribonuclease II activity