ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.2644T>A (p.Cys882Ser) (rs184374817)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000236090 SCV000293225 uncertain significance not provided 2015-10-12 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.2644T>A at the cDNA level, p.Cys882Ser (C882S) at the protein level, and results in the change of a Cysteine to a Serine (TGT>AGT). Using alternate nomenclature, this variant would be defined as BRCA1 2763T>A. This variant has not, to our knowledge, been published in the literature as being pathogenic or benign. BRCA1 Cys882Ser 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 Cysteine and Serine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA1 Cys882Ser occurs at a position that is not conserved and is located in the DNA binding domain and a region known to interact with multiple other proteins (Narod 2004, Paul 2014). 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 Cys882Ser is pathogenic or benign. We consider it to be variant of uncertain significance.
Integrated Genetics/Laboratory Corporation of America RCV000779895 SCV000916789 uncertain significance not specified 2018-07-30 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.2644T>A (p.Cys882Ser) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4.1e-06 in 245886 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2644T>A in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. One ClinVar submission from another clinical diagnostic laboratory (evaluation after 2014) cite the variant as "uncertain significance." Based on the evidence outlined above, the variant was classified as uncertain significance.

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.