ClinGen Dosage Sensitivity Curation Page

FANCB

Curation Status: Complete

Gene Information

Location Information

Evidence for Loss Phenotypes

Evidence for loss of function 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.

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.

Evidence for Triplosenstive Phenotype

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.

NOTE:The loss of function score should be used to evaluate deletions, and the triplosensitivity score should be used to evaluated duplications. CNVs encompassing more than one gene must be evaluated in their totality (e.g. overall size, gain vs. loss, presence of other genes, etc). The rating of a single gene within the CNV should not necessarily be the only criteria by which one defines a clinical interpretation. Individual interpretations must take into account the phenotype described for the patient as well as issues of penetrance and expressivity of the disorder. ACMG has published guidelines for the characterization of postnatal CNVs, and these recommendations should be utilized (Genet Med (2011)13: 680-685). Exceptions to these interpretive correlations will occur, and clinical judgment should always be exercised.