Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000129774 | SCV000184583 | likely benign | Hereditary cancer-predisposing syndrome | 2022-01-04 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Gene |
RCV000478765 | SCV000571146 | uncertain significance | not provided | 2016-07-27 | criteria provided, single submitter | clinical testing | This variant is denoted BRIP1 c.2689A>G at the cDNA level, p.Lys897Glu (K897E) at the protein level, and results in the change of a Lysine to a Glutamic Acid (AAG>GAG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRIP1 Lys897Glu was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Lysine and Glutamic Acid differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRIP1 Lys897Glu occurs at a position that is not conserved and is not located in a known functional domain (Cantor 2011). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available evidence, it is unclear whether BRIP1 Lys897Glu is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. |
| Labcorp Genetics |
RCV001088100 | SCV001048550 | likely benign | Familial cancer of breast; Fanconi anemia complementation group J | 2024-04-01 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV000129774 | SCV001358245 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-06 | criteria provided, single submitter | clinical testing | This missense variant replaces lysine with glutamic acid at codon 897 of the BRIP1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with BRIP1-related disorders in the literature. This variant has been identified in 3/251334 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. |