ClinVar Miner

Submissions for variant NM_007299.4(BRCA1):c.787+1764G>A (rs398122662)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000766566 SCV000209941 uncertain significance not provided 2016-06-27 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.2551G>A at the cDNA level, p.Glu851Lys (E851K) at the protein level, and results in the change of a Glutamic Acid to a Lysine (GAA>AAA). Using alternate nomenclature, this variant would be defined as BRCA1 2670G>A. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA1 Glu851Lys 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 Glutamic Acid and Lysine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA1 Glu851Lys occurs at a position that is conserved across species and is located in the DNA binding domain and region of interaction with RAD51 (Narod 2004, Chen 1998). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, it is unclear whether BRCA1 Glu851Lys is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000159874 SCV000602701 uncertain significance not specified 2016-11-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV000575058 SCV000660996 uncertain significance Hereditary cancer-predisposing syndrome 2017-08-28 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Color RCV000575058 SCV000688389 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-30 criteria provided, single submitter clinical testing
Counsyl RCV000077110 SCV000784873 uncertain significance Breast-ovarian cancer, familial 1 2017-01-18 criteria provided, single submitter clinical testing
Invitae RCV000800458 SCV000940174 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-08-20 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 851 of the BRCA1 protein (p.Glu851Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with breast cancer in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 91593). 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 C15"). 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.
Sharing Clinical Reports Project (SCRP) RCV000077110 SCV000108907 uncertain significance Breast-ovarian cancer, familial 1 2012-05-01 no assertion criteria provided clinical testing

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