ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.6567C>A (p.Asn2189Lys) (rs397507374)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000167273 SCV000218116 uncertain significance Hereditary cancer-predisposing syndrome 2018-03-30 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000167273 SCV000688988 uncertain significance Hereditary cancer-predisposing syndrome 2018-04-23 criteria provided, single submitter clinical testing
Counsyl RCV000239150 SCV000488779 uncertain significance Breast-ovarian cancer, familial 2 2016-06-14 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000160114 SCV000859743 uncertain significance not provided 2018-03-06 criteria provided, single submitter clinical testing
GeneDx RCV000160114 SCV000210394 uncertain significance not provided 2017-09-14 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.6567C>A at the cDNA level, p.Asn2189Lys (N2189K) at the protein level, and results in the change of an Asparagine to a Lysine (AAC>AAA). Using alternate nomenclature, this variant would be defined as BRCA2 6795C>A. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Asn2189Lys was not observed in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Asparagine and Lysine differ in some properties, this is considered a semi-conservative amino acid substitution. BRCA2 Asn2189Lys occurs at a position that is not conserved and is not located in a known functional domain. In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available evidence, it is unclear whether BRCA2 Asn2189Lys is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000458192 SCV000549587 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-12-27 criteria provided, single submitter clinical testing This sequence change replaces asparagine with lysine at codon 2189 of the BRCA2 protein (p.Asn2189Lys). The asparagine residue is weakly conserved and there is a moderate physicochemical difference between asparagine and lysine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a BRCA2-related disease. ClinVar contains an entry for this variant (Variation ID: 182227). 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 lysine amino acid residue is 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, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Sharing Clinical Reports Project (SCRP) RCV000239150 SCV000297545 uncertain significance Breast-ovarian cancer, familial 2 2010-03-03 no assertion criteria provided 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.