Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000546192 | SCV000633520 | likely pathogenic | Familial cancer of breast; Fanconi anemia complementation group J | 2017-09-02 | criteria provided, single submitter | clinical testing | In summary, donor and acceptor splice site variants are typically loss-of-function (PMID: 16199547), and loss-of-function variants in BRIP1 are known to be pathogenic (PMID: 16116423, 17033622, 21964575). However, without additional functional and/or genetic data, this variant has been classified as Likely Pathogenic. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a BRIP1-related disease. This sequence change affects a donor splice site in intron 2 of the BRIP1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. |
| Ambry Genetics | RCV002377045 | SCV002686702 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2022-06-21 | criteria provided, single submitter | clinical testing | The c.93+1G>A intronic variant results from a G to A substitution one nucleotide after coding exon 1 of the BRIP1 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. RNA analysis has shown to cause aberrant splicing in patient-derived lymphoblast cells (Casadei S et al. Proc Natl Acad Sci U S A, 2019 Dec;:). Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic. |
| Myriad Genetics, |
RCV001171457 | SCV004045137 | likely pathogenic | Familial cancer of breast | 2023-05-30 | criteria provided, single submitter | clinical testing | This variant is considered likely pathogenic. This variant occurs within a consensus splice junction and is predicted to result in abnormal mRNA splicing of either an out-of-frame exon or an in-frame exon necessary for protein stability and/or normal function. |
| King Laboratory, |
RCV001171457 | SCV001251368 | pathogenic | Familial cancer of breast | 2019-09-01 | no assertion criteria provided | research |