ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.2935A>G (p.Lys979Glu) (rs730881627)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000212331 SCV000210828 uncertain significance not provided 2018-11-09 criteria provided, single submitter clinical testing This variant is denoted BRIP1 c.2935A>G at the cDNA level, p.Lys979Glu (K979E) at the protein level, and results in the change of a Lysine to a Glutamic Acid (AAA>GAA). This variant was observed in a case of high grade serous ovarian carcinoma as well as in individuals with breast cancer (Ramus 2015, Easton 2016). BRIP1 Lys979Glu was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located within the BRCA1 binding domain (Cantor 2011). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether BRIP1 Lys979Glu is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000160326 SCV000217257 uncertain significance Hereditary cancer-predisposing syndrome 2017-08-11 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (benign)
Invitae RCV000205057 SCV000260094 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2018-10-04 criteria provided, single submitter clinical testing This sequence change replaces lysine with glutamic acid at codon 979 of the BRIP1 protein (p.Lys979Glu). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the literature in an individual affected with ovarian cancer (PMID: 26315354) and in individuals affected with breast cancer (PMID: 26921362). ClinVar contains an entry for this variant (Variation ID: 182336). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: (SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). The glutamic acid amino acid residue is also found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. 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.
Color RCV000160326 SCV000911030 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-29 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.