ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.6847C>G (p.Pro2283Ala) (rs80358909)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000045079 SCV000073092 uncertain significance Hereditary breast and ovarian cancer syndrome 2017-10-11 criteria provided, single submitter clinical testing This sequence change replaces proline with alanine at codon 2283 of the BRCA2 protein (p.Pro2283Ala). The proline residue is highly conserved and there is a small physicochemical difference between proline and alanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA2-related disease. ClinVar contains an entry for this variant (Variation ID: 52213). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly 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.
GeneDx RCV000483877 SCV000566413 uncertain significance not provided 2015-04-28 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.6847C>G at the cDNA level, p.Pro2283Ala (P2283A) at the protein level, and results in the change of a Proline to an Alanine (CCC>GCC). This variant, also published as BRCA2 7075C>G using alternate nomenclature, has been observed in at least one woman with early-onset breast cancer (Malone 2000). BRCA2 Pro2283Ala was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Proline and Alanine differ in some properties, this is considered a semi-conservative amino acid substitution. BRCA2 Pro2283Ala occurs at a position that is conserved across species and is not located in a known functional domain (Roy 2012, Uniprot). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available information, it is unclear whether BRCA2 Pro2283Ala is pathogenic or benign. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000565946 SCV000668550 uncertain significance Hereditary cancer-predisposing syndrome 2017-11-06 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Counsyl RCV000077388 SCV000784782 uncertain significance Breast-ovarian cancer, familial 2 2017-12-29 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077388 SCV000109185 uncertain significance Breast-ovarian cancer, familial 2 2011-11-08 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077388 SCV000146963 uncertain significance Breast-ovarian cancer, familial 2 1998-11-30 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.