Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000130674 | SCV000185560 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-05 | criteria provided, single submitter | clinical testing | The c.380-5A>G intronic variant results from an A to G substitution 5 nucleotides upstream from coding exon 4 in the BRIP1 gene. This nucleotide position is not well conserved in available vertebrate species. In silico splice site analysis for this alteration is inconclusive and 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. |
Invitae | RCV000547580 | SCV000633692 | likely benign | Familial cancer of breast; Fanconi anemia complementation group J | 2023-11-27 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV000547580 | SCV000895118 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000130674 | SCV000903771 | likely benign | Hereditary cancer-predisposing syndrome | 2015-07-27 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000985642 | SCV001134030 | uncertain significance | not provided | 2019-03-07 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000990037 | SCV001140801 | uncertain significance | Familial cancer of breast | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000985642 | SCV001822906 | uncertain significance | not provided | 2020-01-08 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; In-silico analysis, which includes splice predictors and evolutionary conservation, is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown. |
St. |
RCV000990037 | SCV003928152 | uncertain significance | Familial cancer of breast | 2023-04-14 | criteria provided, single submitter | clinical testing | The BRIP1 c.380-5A>G intronic change results in an A to G substitution at the -5 position of intron 4 of the BRIP1 gene. Algorithms that predict the impact of sequence changes on splicing are inconclusive. This variant has a maximum subpopulation frequency of 0.038% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). To our knowledge, this variant has not been reported in individuals with hereditary breast and ovarian cancer syndrome or Fanconi anemia. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. |
Prevention |
RCV004532564 | SCV004115570 | uncertain significance | BRIP1-related disorder | 2023-01-23 | criteria provided, single submitter | clinical testing | The BRIP1 c.380-5A>G variant is predicted to interfere with splicing. To our knowledge, this variant has not been reported in the literature. It is reported in 0.038% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/17-59926622-T-C), which is higher than expected for a primary casue of disease. This variant is classified as a VUS and likely benign by submitters to ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/141947/). Although we suspect that this variant may be benign, at this time, the clinical significance is uncertain due to the absence of conclusive functional and genetic evidence. |