Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000214234 | SCV000274697 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2022-08-30 | criteria provided, single submitter | clinical testing | The c.93+5G>A intronic variant results from a G to A substitution 5 nucleotides after coding exon 1 in 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 studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| Color Diagnostics, |
RCV000214234 | SCV001342456 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-06-08 | criteria provided, single submitter | clinical testing | This variant causes a G to A nucleotide substitution at the +5 position of intron 2 of the BRIP1 gene. Splice site prediction tools predict that this variant may have a significant impact on RNA splicing. This prediction has not been confirmed in published RNA studies. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Labcorp Genetics |
RCV001308700 | SCV001498165 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2022-07-29 | criteria provided, single submitter | clinical testing | Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of exon 2, and is expected to result in the loss of the initiator methionine (Invitae). 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. ClinVar contains an entry for this variant (Variation ID: 230983). This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 2 of the BRIP1 gene. It does not directly change the encoded amino acid sequence of the BRIP1 protein. RNA analysis indicates that this variant induces altered splicing and is likely to result in the loss of the initiator methionine. |
| MGZ Medical Genetics Center | RCV002288861 | SCV002580211 | uncertain significance | Familial cancer of breast | 2021-08-30 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV002288861 | SCV004217139 | uncertain significance | Familial cancer of breast | 2023-03-28 | criteria provided, single submitter | clinical testing |