Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000519853 | SCV000618804 | uncertain significance | not provided | 2018-12-28 | criteria provided, single submitter | clinical testing | The c.1471-3C>G variant in the FANCA gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is predicted to damage the natural splice acceptor site in intron 15, and is expected to cause abnormal gene splicing. However, this nucleotide substitution occurs at a position that is not conserved. The c.1471-3C>G variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret c.1471-3C>G as a variant of uncertain significance. |
Labcorp Genetics |
RCV001065398 | SCV001230354 | uncertain significance | Fanconi anemia | 2021-08-31 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 15 of the FANCA gene. It does not directly change the encoded amino acid sequence of the FANCA protein. It affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with FANCA-related conditions. ClinVar contains an entry for this variant (Variation ID: 450249). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |