Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000116147 | SCV000150056 | uncertain significance | not provided | 2014-01-09 | criteria provided, single submitter | clinical testing | This variant is denoted BRIP1 c.2650T>A at the cDNA level, p.Phe884Ile (F884I) at the protein level, and results in the change of a Phenylalanine to an Isoleucine (TTT>ATT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRIP1 Phe884Ile was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This variant is a conservative substitution of one neutral non-polar amino acid for another, altering a position that is well conserved throughout evolution and is not located in a known functional domain. Multiple in silico algorithms predict that this variant may be damaging to protein structure and function. Based on currently available information, it is unclear whether BRIP1 Phe884Ile is pathogenic or benign. We consider it to be a variant of uncertain significance. Furthermore, BRIP1 has been only recently described in association with cancer predisposition and the risks are not well understood. |
Baylor Genetics | RCV003460837 | SCV004217124 | uncertain significance | Familial cancer of breast | 2023-05-11 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV004601113 | SCV005101043 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-04-22 | criteria provided, single submitter | clinical testing | The p.F884I variant (also known as c.2650T>A), located in coding exon 18 of the BRIP1 gene, results from a T to A substitution at nucleotide position 2650. The phenylalanine at codon 884 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |