ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.655G>A (p.Asp219Asn) (rs273902779)

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
Ambry Genetics RCV000130801 SCV000185697 likely benign Hereditary cancer-predisposing syndrome 2016-11-07 criteria provided, single submitter clinical testing In silico models in agreement (benign);Other strong data supporting benign classification
Counsyl RCV000112756 SCV000488162 uncertain significance Breast-ovarian cancer, familial 1 2016-01-13 criteria provided, single submitter clinical testing
GeneDx RCV000482679 SCV000571058 uncertain significance not provided 2016-07-18 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.655G>A at the cDNA level, p.Asp219Asn (D219N) at the protein level, and results in the change of an Aspartic Acid to an Asparagine (GAT>AAT). Using alternate nomenclature, this variant would be defined as BRCA1 774G>A. This variant has been reported in an individual with a Lynch syndrome-associated tumor and/or colon polyps (Yurgelun 2015). BRCA1 Asp219Asn 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 Aspartic Acid and Asparagine differ in some properties, this is considered a semi-conservative amino acid substitution. BRCA1 Asp219Asn occurs at a position that is not conserved and is located in a region known to interact with BRD7 and MB2 (Wang 1998, Harte 2010). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available evidence, it is unclear whether BRCA1 Asp219Asn is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Color Health, Inc RCV000130801 SCV000909403 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-06 criteria provided, single submitter clinical testing
Invitae RCV001341240 SCV001535100 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-09-19 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 219 of the BRCA1 protein (p.Asp219Asn). The aspartic acid residue is weakly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs273902779, ExAC 0.01%). This variant has been observed in an individual affected with suspected Lynch syndrome (PMID: 25980754). ClinVar contains an entry for this variant (Variation ID: 55655). Experimental studies have shown that this missense change does not affect E3 ubiquitin ligase activity of BRCA1 (PMID: 25823446). 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.
Breast Cancer Information Core (BIC) (BRCA1) RCV000112756 SCV000145646 uncertain significance Breast-ovarian cancer, familial 1 2010-12-17 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.