FANCB

• Haploinsufficiency score: 3
• Strength of Evidence (disclaimer): Sufficient evidence for dosage pathogenicity
• Haploinsufficiency Phenotype: FANCONI ANEMIA, COMPLEMENTATION GROUP B; FANCB

Evidence for haploinsufficiency phenotype

PubMed ID	Description
15502827	In an individual (EUFA178) with Fanconi anemia of complementation group B, Meetei et al. (2004) found a 3,314-bp deletion of the FANCB gene that included the promoter region and exon 1 (10693del3314). The mother and sister of the proband were carriers.
15502827	In cells derived from an individual (HSC230) with Fanconi anemia of complementation group B, Meetei et al. (2004) found a frameshift mutation (1838insT) in exon 8 of the FANCB gene, resulting in a premature stop codon.
16679491	In a fetus with Fanconi anemia who presented with the VACERL with hydrocephalus phenotype, Holden et al. (2006) found a splice site mutation (IVS7DS+5G-A) in intron 7 of the FANCB gene. Sequencing of the mutant cDNA fragment from the affected fetus showed that this mutation caused skipping of exon 7 and a frameshift with a stop codon at position 446. The mother and maternal grandmother were heterozygous for the mutation and showed preferential X-inactivation of the mutant FANCB allele.

Haploinsufficiency phenotype comments:

Heterozygous mutations of FANCB cause Fanconi anemia of complementation group B.

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.

• Triplosensitivity score: 0
• Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.