ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.1843TCT[1] (p.Ser616del) (rs80358329)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 21
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031011 SCV001161491 benign Breast-ovarian cancer, familial 1 2019-06-18 reviewed by expert panel curation IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 5.40E-06
Invitae RCV000047608 SCV000075621 benign Hereditary breast and ovarian cancer syndrome 2020-12-06 criteria provided, single submitter clinical testing
Counsyl RCV000031011 SCV000154019 likely benign Breast-ovarian cancer, familial 1 2014-02-05 criteria provided, single submitter literature only
Ambry Genetics RCV000131329 SCV000186303 benign Hereditary cancer-predisposing syndrome 2014-11-18 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Michigan Medical Genetics Laboratories,University of Michigan RCV000031011 SCV000195894 benign Breast-ovarian cancer, familial 1 2016-04-21 criteria provided, single submitter clinical testing
GeneDx RCV000249365 SCV000209931 likely benign not specified 2018-02-05 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
PreventionGenetics,PreventionGenetics RCV000249365 SCV000311786 likely benign not specified criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000031011 SCV000575706 uncertain significance Breast-ovarian cancer, familial 1 2015-08-27 criteria provided, single submitter clinical testing
Institute for Biomarker Research,Medical Diagnostic Laboratories, L.L.C. RCV000047608 SCV000576445 likely benign Hereditary breast and ovarian cancer syndrome 2017-02-14 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000249365 SCV000600269 likely benign not specified 2017-04-01 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000249365 SCV000602730 likely benign not specified 2017-02-21 criteria provided, single submitter clinical testing
Color Health, Inc RCV000131329 SCV000682991 likely benign Hereditary cancer-predisposing syndrome 2014-12-16 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000031011 SCV000744671 uncertain significance Breast-ovarian cancer, familial 1 2017-05-31 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000679684 SCV000806901 likely benign not provided 2016-04-25 criteria provided, single submitter clinical testing
Mendelics RCV000047608 SCV000839279 likely benign Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000679684 SCV000888852 benign not provided 2018-05-11 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000769722 SCV000901143 likely benign Breast and/or ovarian cancer 2017-08-30 criteria provided, single submitter clinical testing
Mendelics RCV000031011 SCV001140594 likely benign Breast-ovarian cancer, familial 1 2019-05-28 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031011 SCV000053604 benign Breast-ovarian cancer, familial 1 2012-05-01 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000031011 SCV000144201 uncertain significance Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000679684 SCV001549176 likely benign not provided no assertion criteria provided clinical testing The BRCA1 p.Ser616del variant is an in-frame deletion resulting in the removal of a serine (Ser) residue at position 616; the impact of this alteration on BRCA1 protein function is not known. It has been identified in the literature in 9 of 6508 proband chromosomes (frequency: 0.001) from Nigerian, Sudanese, Moroccan, British and African- American individuals with breast cancer and HBOC and was present in 3 of the 506 control chromosomes (frequency: 0.006) from healthy individuals (Fackenthal 2012, Biunno 2014, Borg 2010, Ellis 2000, Judkins 2005a, McKean-Cowdin 2005, Tazzite 2012). The variant was identified in control databases in 103 of 282534 chromosomes (0 homozygous) at a frequency of 0.0003646, and was observed at the highest frequency in the African population in 97 of 24900 chromosomes (freq: 0.003896) (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was identified in ClinVar (Benign, reviewed by expert panel. Classified as benign by ENIGMA, Ambry Genetics, Michigan Medical Genetics Laboratories, Quest Diagnostics, Invitae, SCRP. Classified as likely benign by ARUP Laboratories, GeneDx, Michigan Medical Genetics Laboratories, Mendelics, CHEO, Color, Institute for Biomarker Research Medical Diagnostic Laboratories, Prevention Genetics, Quest Diagnostics. Classified as VUS by Fulgent, BIC). The variant was also identified in dbSNP (ID: rs rs80358329), ARUP Laboratories BRCA Mutations Database (classification definitely pathogenic based on a publication from 2000), and UMD (3X with “unclassified variant” classification). Myriad classifies this as a polymorphism (personal communication). The variant was identified with a co-occurring pathogenic BRCA1 variant (1755del19), increasing the likelihood that the p.Ser616del variant does not have clinical significance (Judkins 2005). The deletion variant localizes to a highly conserved region that interacts with several regulating proteins, however, it was found to occur in both affected and unaffected siblings in an African-American sibship (McKean-Cowdin 2005), but was not identified in controls in a British study looking at BRCA1 mutations in early onset/no family history of breast/ovarian cancer cases (Ellis 2000). In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

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.