ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.2466T>G (p.Asn822Lys)

dbSNP: rs1064794701
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000482739 SCV000569759 uncertain significance not provided 2016-10-17 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.2466T>G at the cDNA level, p.Asn822Lys (N822K) at the protein level, and results in the change of an Asparagine to a Lysine (AAT>AAG). Using alternate nomenclature, this variant would be defined as BRCA1 2585T>G. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA1 Asn822Lys 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 Asparagine and Lysine differ in some properties, this is considered a semi-conservative amino acid substitution. BRCA1 Asn822Lys occurs at a position that is not conserved and is located in the DNA binding domain and binding domain with RAD51 (Chen 1998, Narod 2004). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether BRCA1 Asn822Lys is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
University of Washington Department of Laboratory Medicine, University of Washington RCV003157580 SCV003847650 likely benign Hereditary cancer-predisposing syndrome 2023-03-23 criteria provided, single submitter curation Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
Ambry Genetics RCV003157580 SCV005547410 uncertain significance Hereditary cancer-predisposing syndrome 2024-09-04 criteria provided, single submitter clinical testing The p.N822K variant (also known as c.2466T>G), located in coding exon 9 of the BRCA1 gene, results from a T to G substitution at nucleotide position 2466. The asparagine at codon 822 is replaced by lysine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.

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.