Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000546037 | SCV000633686 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2022-11-01 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu1222Glyfs*7) in the BRIP1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 28 amino acid(s) of the BRIP1 protein. This variant is present in population databases (rs752586524, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 461162). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |
| Ambry Genetics | RCV000567587 | SCV000673159 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-10-10 | criteria provided, single submitter | clinical testing | The c.3664dupG variant, located in coding exon 19 of the BRIP1 gene, results from a duplication of G at nucleotide position 3664, causing a translational frameshift with a predicted alternate stop codon (p.E1222Gfs*7). Frameshifts are typically deleterious in nature, however, this frameshift occurs at the 3' terminus of BRIP1, is not expected to trigger nonsense-mediated mRNA decay, and removes only the last 21 amino acids of the protein. The exact functional impact of these removed amino acids is unknown at this time; however, structural and functional studies suggest that at least two residues contained in this deleted region (Ser1237 and Lys1249) have functional importance (Olsen JV et al. Sci Signal. 2010 Jan; 3(104):ra3; Xie J et al. PLoS Genet. Jul 2012; 8(7): e1002786). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000985640 | SCV001134027 | uncertain significance | not provided | 2019-02-12 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV000567587 | SCV001358462 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-09-25 | criteria provided, single submitter | clinical testing | This variant inserts 1 nucleotide in exon 20 of the BRIP1 gene, creating a frameshift and premature translation stop signal in the last coding exon. This mutant transcript is predicted to escape nonsense-mediated decay and be expressed as a truncated protein. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 11/282168 chromosomes 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. |
| Baylor Genetics | RCV004568779 | SCV005059223 | uncertain significance | Familial cancer of breast | 2024-03-10 | criteria provided, single submitter | clinical testing | |
| 3DMed Clinical Laboratory Inc | RCV000677869 | SCV000804030 | uncertain significance | Breast neoplasm | 2018-01-10 | no assertion criteria provided | clinical testing |