Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000552945 | SCV000626232 | uncertain significance | Fanconi anemia | 2017-05-10 | criteria provided, single submitter | clinical testing | In summary, this is a novel intronic change with uncertain impact on splicing. It has been classified as a Variant of Uncertain Significance. Nucleotide substitutions within the consensus splice site are relatively common causes of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of nucleotide changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a FANCC-related disease. This sequence change falls in intron 12 of the FANCC gene. It does not directly change the encoded amino acid sequence of the FANCC protein, but it affects a nucleotide within the consensus splice site of the intron. |
Ambry Genetics | RCV002367773 | SCV002625987 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-21 | criteria provided, single submitter | clinical testing | The c.1154+2dupT intronic variant, results from a duplication of one nucleotide at nucleotide position c.1154+2 after intron 11 of the FANCC gene. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site; however, direct evidence is insufficient at this time (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Gene |
RCV003322780 | SCV004027932 | likely pathogenic | not provided | 2023-02-16 | criteria provided, single submitter | clinical testing | Creates an intronic +5 splice site variant (G>A) in a gene for which loss of function is a known mechanism of disease, and splice predictors support a deleterious effect; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge |