FANCD2

FA complementation group D2, the group of FA complementation groups|Armadillo like helical domain containing

Basic information

Region (hg38): 3:10026369-10101932

Previous symbols: [ "FACD", "FANCD" ]

Links

ENSG00000144554 ∙ NCBI:2177 ∙ OMIM:613984 ∙ HGNC:3585 ∙ Uniprot:Q9BXW9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Fanconi anemia complementation group D2 (Definitive), mode of inheritance: AR
• Fanconi anemia complementation group D2 (Definitive), mode of inheritance: AR
• Fanconi anemia complementation group D2 (Strong), mode of inheritance: AR
• Fanconi anemia (Supportive), mode of inheritance: AR
• Fanconi anemia complementation group D2 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Fanconi anemia, complementation group D2	AR	Allergy/Immunology/Infectious; Cardiovascular; Hematologic; Oncologic	Specific treatments can help manifestations (eg, oral androgens for blood counts; G-CSF for neutrophil count); HSCT can be curative, but solid tumor risk may remain; Surveillance for complications such as bone marrow failure is recommended; Fanconi anemia can involve congenital cardiac (and other) anomalies, and awareness may allow early management	Audiologic/Otolaryngologic; Allergy/Immunology/Infectious; Cardiovascular; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic; Renal	17436244; 20301575; 22720145; 23285130

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FANCD2 gene.

• Fanconi anemia (1032 variants)
• Fanconi anemia complementation group D2 (361 variants)
• not provided (260 variants)
• not specified (123 variants)
• Hereditary breast ovarian cancer syndrome (74 variants)
• Inborn genetic diseases (33 variants)
• Fanconi anemia complementation group A (17 variants)
• Ovarian cancer (9 variants)
• FANCD2-related condition (5 variants)
• Hepatoblastoma (2 variants)
• Hereditary cancer (1 variants)
• See cases (1 variants)
• Malignant tumor of breast (1 variants)
• Intellectual disability;Global developmental delay;Cleft palate (1 variants)
• Pituitary stalk interruption syndrome (1 variants)
• Acute myeloid leukemia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FANCD2 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		1	11	213	10	235
missense	1	3	443	18	2	467
nonsense	23	30	2			55
start loss						0
frameshift	24	34	4			62
inframe indel			13			13
splice donor/acceptor (+/-2bp)	6	33	2			41
splice region		2	40	48	1	91
non coding			24	203	119	346
Total	54	101	499	434	131

Highest pathogenic variant AF is 0.000177

Variants in FANCD2

This is a list of pathogenic ClinVar variants found in the FANCD2 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-10026743-GCCAGATGGTA-G			Benign (Oct 18, 2018)
3-10028612-G-A		Fanconi anemia complementation group D2	Uncertain significance (Jan 12, 2018)
3-10028652-G-C		Fanconi anemia complementation group D2 • Hereditary breast ovarian cancer syndrome	Benign/Likely benign (Jul 07, 2023)
3-10028659-T-C		Fanconi anemia complementation group D2	Pathogenic (Feb 28, 2020)
3-10028676-C-T		Fanconi anemia	Likely benign (Dec 28, 2023)
3-10028677-T-A		Inborn genetic diseases	Uncertain significance (May 11, 2022)
3-10028685-T-C		Fanconi anemia • Fanconi anemia complementation group D2	Uncertain significance (Jan 24, 2024)
3-10028690-G-A		Fanconi anemia complementation group D2 • Fanconi anemia • not specified • FANCD2-related disorder	Conflicting classifications of pathogenicity (Jan 29, 2024)
3-10028692-A-T		Fanconi anemia complementation group D2 • Fanconi anemia	Uncertain significance (Feb 24, 2022)
3-10028693-TAA-T		Fanconi anemia	Pathogenic (Apr 15, 2023)
3-10028693-T-TA		Fanconi anemia complementation group D2	Likely pathogenic (-)
3-10028695-A-G		Fanconi anemia	Uncertain significance (Apr 24, 2022)
3-10028701-G-C		Fanconi anemia	Uncertain significance (Mar 18, 2022)
3-10028702-C-T		Fanconi anemia	Likely benign (Dec 11, 2023)
3-10028715-G-A		Fanconi anemia	Uncertain significance (Aug 28, 2021)
3-10028717-C-T		Fanconi anemia	Likely benign (Nov 05, 2023)
3-10028719-C-G		Fanconi anemia	Uncertain significance (Dec 23, 2021)
3-10028721-AGT-A		Fanconi anemia	Likely pathogenic (Dec 21, 2023)
3-10028723-T-G		Fanconi anemia • Fanconi anemia complementation group D2	Likely pathogenic (Feb 18, 2022)
3-10028726-GTATC-G		Fanconi anemia	Likely benign (Aug 09, 2023)
3-10028728-A-G		Fanconi anemia	Likely benign (Mar 23, 2023)
3-10028729-T-C		Fanconi anemia	Likely benign (Jul 31, 2023)
3-10028731-T-G		Fanconi anemia	Likely benign (Nov 21, 2023)
3-10028733-G-C		not specified • Fanconi anemia complementation group D2 • Hereditary breast ovarian cancer syndrome • Fanconi anemia	Benign (Feb 01, 2024)
3-10028868-G-C			Likely benign (Mar 20, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FANCD2	protein_coding	protein_coding	ENST00000287647	42	75517

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.10e-30	0.426	125570	0	178	125748	0.000708

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0373	735	738	0.996	0.0000377	9656
Missense in Polyphen		162	206.82	0.78327		2871
Synonymous	0.529	264	275	0.959	0.0000144	2737
Loss of Function	2.42	60	83.9	0.715	0.00000439	1022

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00216	0.00214
Ashkenazi Jewish	0.000695	0.000695
East Asian	0.000652	0.000653
Finnish	0.000556	0.000554
European (Non-Finnish)	0.000686	0.000686
Middle Eastern	0.000652	0.000653
South Asian	0.000523	0.000523
Other	0.000815	0.000815

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for maintenance of chromosomal stability. Promotes accurate and efficient pairing of homologs during meiosis. Involved in the repair of DNA double-strand breaks, both by homologous recombination and single-strand annealing. May participate in S phase and G2 phase checkpoint activation upon DNA damage. Plays a role in preventing breakage and loss of missegregating chromatin at the end of cell division, particularly after replication stress. Required for the targeting, or stabilization, of BLM to non-centromeric abnormal structures induced by replicative stress. Promotes BRCA2/FANCD1 loading onto damaged chromatin. May also be involved in B-cell immunoglobulin isotype switching. {ECO:0000269|PubMed:11239453, ECO:0000269|PubMed:11239454, ECO:0000269|PubMed:12086603, ECO:0000269|PubMed:12239151, ECO:0000269|PubMed:14517836, ECO:0000269|PubMed:15115758, ECO:0000269|PubMed:15314022, ECO:0000269|PubMed:15377654, ECO:0000269|PubMed:15454491, ECO:0000269|PubMed:15650050, ECO:0000269|PubMed:15661754, ECO:0000269|PubMed:15671039, ECO:0000269|PubMed:19465921}.
• Disease: DISEASE: Fanconi anemia complementation group D2 (FANCD2) [MIM:227646]: A disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. It is associated with cardiac, renal and limb malformations, dermal pigmentary changes, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair. {ECO:0000269|PubMed:11239453}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Fanconi anemia pathway - Homo sapiens (human);miRNA Regulation of DNA Damage Response;TP53 Regulates Transcription of DNA Repair Genes;DNA Damage Response;Fanconi Anemia Pathway;DNA Repair;Gene expression (Transcription);role of brca1 brca2 and atr in cancer susceptibility;brca1 dependent ub ligase activity;Generic Transcription Pathway;RNA Polymerase II Transcription;TP53 Regulates Transcription of DNA Repair Genes;Fanconi anemia pathway;Transcriptional Regulation by TP53;TNFalpha;BARD1 signaling events;ATM pathway;ATR signaling pathway (Consensus)

Intolerance Scores

• loftool: 0.989
• rvis_EVS: -0.92
• rvis_percentile_EVS: 9.79

Haploinsufficiency Scores

• pHI: 0.250
• hipred: Y
• hipred_score: 0.661
• ghis: 0.635

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.928

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Fancd2
• Phenotype: neoplasm; 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); reproductive system phenotype; hematopoietic system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: DNA repair;synapsis;gamete generation;response to gamma radiation;cellular response to oxidative stress;interstrand cross-link repair;regulation of regulatory T cell differentiation;brain morphogenesis;regulation of inflammatory response;regulation of DNA-binding transcription factor activity;neuronal stem cell population maintenance;regulation of CD40 signaling pathway
• Cellular component: condensed chromosome;nucleus;nucleoplasm;nucleolus;cytosol;nuclear body
• Molecular function: protein binding;DNA polymerase binding