Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000216911 | SCV000277420 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2023-06-12 | criteria provided, single submitter | clinical testing | The c.2905+1G>A intronic variant results from a G to A substitution one nucleotide after coding exon 18 of the BRIP1 gene. This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein. As such, this alteration is classified as likely pathogenic. |
Labcorp Genetics |
RCV000555856 | SCV000633512 | likely pathogenic | Familial cancer of breast; Fanconi anemia complementation group J | 2017-10-14 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in BRIP1 are known to be pathogenic (PMID: 16116423, 17033622, 21964575). This variant has not been reported in the literature in individuals with BRIP1-related disease. ClinVar contains an entry for this variant (Variation ID: 233111). This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 19 of the BRIP1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. |
Counsyl | RCV000663077 | SCV000786151 | likely pathogenic | Fanconi anemia complementation group J; Ovarian neoplasm | 2018-03-09 | criteria provided, single submitter | clinical testing | |
Myriad Genetics, |
RCV003316227 | SCV004019327 | likely pathogenic | Familial cancer of breast | 2023-02-27 | 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. |