FANCA

FA complementation group A, the group of FA core complex|FA complementation groups

Basic information

Region (hg38): 16:89726683-89816977

Previous symbols: [ "FACA", "FANCH" ]

Links

ENSG00000187741 ∙ NCBI:2175 ∙ OMIM:607139 ∙ HGNC:3582 ∙ Uniprot:O15360 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

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

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Fanconi anemia, complementation group A	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	13826667; 6338978; 2571931; 1536187; 1521091; 8502512; 8081006; 8781414; 9371798; 10094191; 11389461; 14504102; 14605744; 17105750; 20301575; 20507306; 21273304; 22480464; 22950077; 23067021; 23898106; 23973728

ClinVar

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

• Fanconi anemia (291 variants)
• Fanconi anemia complementation group A (133 variants)
• not provided (27 variants)
• FANCA-related disorder (7 variants)
• not specified (2 variants)
• See cases (2 variants)
• Pituitary stalk interruption syndrome (1 variants)
• Neuroblastoma (1 variants)
• Inborn genetic diseases (1 variants)
• Abnormality of blood and blood-forming tissues (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FANCA 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			13	976	7	996
missense	6	38	1217	58	9	1328
nonsense	113	80	4	1		198
start loss	6	2				8
frameshift	152	100	7			259
inframe indel	2	4	24			30
splice donor/acceptor (+/-2bp)	42	152	7	1		202
splice region	2	5	126	232	8	373
non coding		2	52	740	177	971
Total	321	378	1324	1776	193

Highest pathogenic variant AF is 0.0000920

Variants in FANCA

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

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

Position	Type	Phenotype	Significance	ClinVar
16-89727312-C-A		not specified	Uncertain significance (Sep 28, 2022)
16-89727313-C-G			Likely benign (Jul 01, 2023)
16-89727323-C-T			Likely benign (Feb 01, 2023)
16-89727335-G-A		not specified	Uncertain significance (Apr 22, 2024)
16-89729240-T-C		not specified	Uncertain significance (Dec 01, 2022)
16-89729252-A-G		not specified	Uncertain significance (Jan 31, 2024)
16-89729285-C-T		not specified	Uncertain significance (May 26, 2023)
16-89729290-G-A		not specified	Uncertain significance (May 17, 2023)
16-89729302-C-G		not specified	Uncertain significance (May 26, 2024)
16-89729315-G-T		not specified	Uncertain significance (Oct 10, 2023)
16-89733308-T-C			Likely benign (Feb 01, 2023)
16-89733317-G-T		not specified	Uncertain significance (Jan 05, 2022)
16-89733334-C-T		not specified	Uncertain significance (Apr 07, 2023)
16-89733384-G-A		not specified	Uncertain significance (May 05, 2023)
16-89733402-C-T		not specified	Uncertain significance (Nov 28, 2023)
16-89733505-A-G		not specified	Uncertain significance (May 11, 2022)
16-89733525-A-C		not specified	Uncertain significance (Mar 28, 2022)
16-89733534-T-C		not specified	Uncertain significance (Sep 01, 2023)
16-89733942-G-A		not specified	Uncertain significance (May 21, 2024)
16-89733951-C-T		not specified	Uncertain significance (May 24, 2023)
16-89734003-G-A		not specified	Uncertain significance (May 15, 2023)
16-89737589-T-C		Fanconi anemia complementation group A	Uncertain significance (Jan 12, 2018)
16-89737590-G-A		Fanconi anemia complementation group A	Benign (Jan 12, 2018)
16-89737615-C-T		Fanconi anemia complementation group A	Benign (Jan 13, 2018)
16-89737664-T-C		Fanconi anemia complementation group A	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FANCA	protein_coding	protein_coding	ENST00000389301	43	79109

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.59e-68	4.78e-13	125478	0	270	125748	0.00107

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-5.41	1202	777	1.55	0.0000482	9398
Missense in Polyphen		41	31.281	1.3107		289
Synonymous	-8.03	506	322	1.57	0.0000218	2907
Loss of Function	-1.29	96	83.3	1.15	0.00000424	952

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00240	0.00240
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.00148	0.00147
Finnish	0.000185	0.000185
European (Non-Finnish)	0.00126	0.00126
Middle Eastern	0.00148	0.00147
South Asian	0.00114	0.00114
Other	0.000489	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: DNA repair protein that may operate in a postreplication repair or a cell cycle checkpoint function. May be involved in interstrand DNA cross-link repair and in the maintenance of normal chromosome stability.
• Disease: DISEASE: Fanconi anemia, complementation group A (FANCA) [MIM:227650]: 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:10094191, ECO:0000269|PubMed:10210316, ECO:0000269|PubMed:10521298, ECO:0000269|PubMed:10807541, ECO:0000269|PubMed:11091222, ECO:0000269|PubMed:17924555, ECO:0000269|PubMed:9371798, ECO:0000269|PubMed:9399890, ECO:0000269|PubMed:9929978}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Fanconi anemia pathway - Homo sapiens (human);Fanconi Anemia Pathway;DNA Repair;role of brca1 brca2 and atr in cancer susceptibility;brca1 dependent ub ligase activity;Fanconi anemia pathway;BARD1 signaling events (Consensus)

Recessive Scores

• pRec: 0.243

Intolerance Scores

• loftool: 0.0821
• rvis_EVS: -0.1
• rvis_percentile_EVS: 45.67

Haploinsufficiency Scores

• pHI: 0.234
• hipred: Y
• hipred_score: 0.566
• ghis: 0.590

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.985

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Fanca
• 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); reproductive system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; embryo phenotype; skeleton phenotype; vision/eye phenotype; craniofacial phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: DNA repair;male meiotic nuclear division;male gonad development;female gonad development;interstrand cross-link repair;regulation of cell population proliferation;regulation of regulatory T cell differentiation;regulation of inflammatory response;regulation of DNA-binding transcription factor activity;protein-containing complex assembly;regulation of CD40 signaling pathway
• Cellular component: nucleus;nucleoplasm;cytoplasm;Fanconi anaemia nuclear complex
• Molecular function: protein binding