Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000565993 | SCV000666183 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-05-22 | criteria provided, single submitter | clinical testing | The c.2905+4T>C intronic variant results from a T to C substitution 4 nucleotides after coding exon 18 in the BRIP1 gene. This nucleotide position is well conserved in available vertebrate species. Using the BDGP splice site prediction tool, this alteration is predicted to weaken the native splice donor site; however, direct evidence is unavailable. The ESEfinder splice prediction software does not produce a reliable prediction for the nearby native splice donor site. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV000636100 | SCV000757532 | uncertain significance | Familial cancer of breast; Fanconi anemia, complementation group J | 2019-12-11 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 19 of the BRIP1 gene. It does not directly change the encoded amino acid sequence of the BRIP1 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs373835270, ExAC 0.002%). This variant has not been reported in the literature in individuals with BRIP1-related disease. ClinVar contains an entry for this variant (Variation ID: 481621). Nucleotide substitutions within 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 is not likely to affect RNA splicing, but this prediction has not been confirmed by published transcriptional studies. 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. |
| Color | RCV000565993 | SCV001347675 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-09-06 | criteria provided, single submitter | clinical testing |