Fanconi anemia complementation group A: genes and variants

Genes linked to Fanconi anemia complementation group A

• FANCA: Fanconi anemia group A protein

  It helps assemble the Fanconi-anemia core complex that monoubiquitinates FANCD2 and FANCI after DNA interstrand crosslinks stall replication. Biallelic loss-of-function variants are the most common cause of Fanconi anemia, with bone-marrow failure and cancer predisposition.

  38 disease-causing and 265 uncertain variants in FANCA are linked to Fanconi anemia complementation group A.

• BRCA1: Breast cancer type 1 susceptibility protein

  It coordinates DNA-damage signaling and homologous-recombination repair while helping protect stalled replication forks and chromosome integrity. Germline loss-of-function variants strongly predispose to breast and ovarian cancer and increase risk for several other malignancies.

  0 disease-causing and 0 uncertain variants in BRCA1 are linked to Fanconi anemia complementation group A.

• FANCC: Fanconi anemia group C protein

  It contributes to activation of the FANCD2-FANCI DNA-repair pathway after replication-blocking lesions. Biallelic loss-of-function variants cause Fanconi anemia group C, with chromosome instability, marrow failure, congenital abnormalities, and elevated cancer risk.

  0 disease-causing and 4 uncertain variants in FANCC are linked to Fanconi anemia complementation group A.

Weakly linked (only a few uncertain records): FANCD2.

Known disease-causing variants in Fanconi anemia complementation group A

Which prediction tools work for Fanconi anemia complementation group A

How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).

• MetaLR: 98 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• AlphaMissense: 97 out of 100
• CATVariant: 96 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• EVE: 95 out of 100
• CADD: 94 out of 100
• REVEL: 93 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• PolyPhen-2: 92 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 91 out of 100
• phyloP: 90 out of 100
• MutPred2: 76 out of 100 (learned from overlapping clinical labels, so this is optimistic)

Same protein, different disease

• Fanconi anemia is also caused by FANCA variants; they fall partly in the same places as the Fanconi anemia complementation group A variants (15 disease-causing).

Diseases related to Fanconi anemia complementation group A

• Ovarian cancer, also linked to BRCA1, FANCA and FANCC
• Acute myeloid leukemia, also linked to FANCA and FANCC
• Fanconi anemia, also linked to FANCA and FANCC
• Hereditary breast ovarian cancer syndrome, also linked to BRCA1 and FANCC
• Breast-ovarian cancer, familial, susceptibility to, 1, also linked to BRCA1
• Ovarian neoplasm, also linked to BRCA1
• Myelodysplastic syndrome, also linked to FANCC
• Familial pancreatic carcinoma, also linked to BRCA1
• Fanconi anemia complementation group C, also linked to FANCC

Frequently asked questions

Which genes are linked to Fanconi anemia complementation group A?

In CATVariant, Fanconi anemia complementation group A is linked to 3 analyzed proteins: FANCA (Fanconi anemia group A protein), BRCA1 (Breast cancer type 1 susceptibility protein) and FANCC (Fanconi anemia group C protein).

How many genetic variants are linked to Fanconi anemia complementation group A?

389 variants: 38 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 272 are of uncertain significance or have conflicting reports.

Which uncertain variants in Fanconi anemia complementation group A look disease-causing?

None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.

Which variant effect predictor works best for Fanconi anemia complementation group A?

Among tools not trained on clinical labels, AlphaMissense separates this disease's known disease-causing variants from harmless ones best (AUROC 0.97, based on 17 disease-causing and 14 harmless variants).

About this data

Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.

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