Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000568422 | SCV000666212 | uncertain significance | Hereditary cancer-predisposing syndrome | 2016-03-29 | criteria provided, single submitter | clinical testing | The p.K528E variant (also known as c.1582A>G), located in coding exon 10 of the BRIP1 gene, results from an A to G substitution at nucleotide position 1582. The lysine at codon 528 is replaced by glutamic acid, an amino acid with similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6500 samples (13000 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 120000 alleles tested) in our clinical cohort. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. |
| Labcorp Genetics |
RCV001858188 | SCV002199612 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2021-03-27 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. This variant has not been reported in the literature in individuals with BRIP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 481635). This variant is present in population databases (rs748962730, ExAC 0.006%). This sequence change replaces lysine with glutamic acid at codon 528 of the BRIP1 protein (p.Lys528Glu). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and glutamic acid. |
| Center for Genomic Medicine, |
RCV003493655 | SCV004242903 | uncertain significance | not specified | 2024-02-06 | criteria provided, single submitter | clinical testing |