ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9218A>G (p.Asp3073Gly) (rs80359186)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130237 SCV000185079 uncertain significance Hereditary cancer-predisposing syndrome 2019-03-17 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
GeneDx RCV000656811 SCV000329147 uncertain significance not provided 2017-08-29 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.9218A>G at the cDNA level, p.Asp3073Gly (D3073G) at the protein level, and results in the change of an Aspartic Acid to a Glycine (GAC>GGC). Also published as BRCA2 9446A>G using alternate nomenclature, this variant has been observed in at least one individual with family history of breast and/or ovarian cancer (Weber 2006, Houdayer 2012). A homology-directed DNA break repair assay demonstrated that this variant results in reduced homologous recombination repair activity compared to wildtype (Guidugli 2013). BRCA2 Asp3073Gly was not observed at a significant allele frequency in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Aspartic Acid and Glycine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA2 Asp3073Gly occurs at a position that is conserved across species and is located in the DNA binding domain (Yang 2002). While protein-based in silico analyses predict that this variant is probably damaging to protein structure and function, multiple splicing models predict that this variant may create a cryptic splice donor site and lead to abnormal splicing. However, Houdayer et al. (2012) performed RNA analysis and reported that this variant had no effect on splicing. Based on currently available evidence, it is unclear whether BRCA2 Asp3073Gly is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000326170 SCV000600849 uncertain significance not specified 2017-06-14 criteria provided, single submitter clinical testing
Color RCV000130237 SCV000684035 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-08 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000765143 SCV000896369 uncertain significance Familial cancer of breast; Breast-ovarian cancer, familial 2; Fanconi anemia, complementation group D1; Medulloblastoma; Wilms tumor 1; Malignant tumor of prostate; Pancreatic cancer 2; Glioma susceptibility 3 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000045750 SCV000073763 uncertain significance Hereditary breast and ovarian cancer syndrome 2014-06-11 no assertion criteria provided clinical testing The interpretation for this sequence variant was made by Invitae based on the ACMG guidelines.
Sharing Clinical Reports Project (SCRP) RCV000077464 SCV000109262 uncertain significance Breast-ovarian cancer, familial 2 2012-12-17 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077464 SCV000147570 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 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.