ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.978C>A (p.Ser326Arg) (rs28897706)

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Total submissions: 28
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000077475 SCV000244497 benign Breast-ovarian cancer, familial 2 2015-08-10 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 = 0.000583
Invitae RCV000045896 SCV000073909 benign Hereditary breast and ovarian cancer syndrome 2020-12-06 criteria provided, single submitter clinical testing
CSER _CC_NCGL, University of Washington RCV000148427 SCV000190126 likely benign Breast neoplasm 2014-06-01 criteria provided, single submitter research
Michigan Medical Genetics Laboratories,University of Michigan RCV000077475 SCV000195956 benign Breast-ovarian cancer, familial 2 2014-11-03 criteria provided, single submitter clinical testing
Ambry Genetics RCV000162581 SCV000212997 benign Hereditary cancer-predisposing syndrome 2014-11-19 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.
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000768586 SCV000219297 likely benign Breast and/or ovarian cancer 2015-09-16 criteria provided, single submitter clinical testing
Counsyl RCV000077475 SCV000220357 benign Breast-ovarian cancer, familial 2 2014-05-29 criteria provided, single submitter literature only
Illumina Clinical Services Laboratory,Illumina RCV000077475 SCV000383624 likely benign Breast-ovarian cancer, familial 2 2019-04-18 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Clinical Services Laboratory,Illumina RCV000354967 SCV000383625 likely benign Fanconi anemia, complementation group D1 2019-04-18 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000444014 SCV000511127 uncertain significance not provided 2016-07-29 criteria provided, single submitter clinical testing Converted during submission to Uncertain significance.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000120308 SCV000538481 uncertain significance not specified 2016-03-28 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Multiple publications classify as VUS/not pathogenic; ExAC: 0.1% (83/72816) of European chromosomes (Finnish and Non-Finnish)
Cancer Genetics and Genomics Laboratory,British Columbia Cancer Agency RCV000120308 SCV000586921 benign not specified 2017-04-18 criteria provided, single submitter clinical testing
Color Health, Inc RCV000162581 SCV000684091 likely benign Hereditary cancer-predisposing syndrome 2015-01-14 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000077475 SCV000743254 benign Breast-ovarian cancer, familial 2 2014-10-09 criteria provided, single submitter clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000077475 SCV000744399 benign Breast-ovarian cancer, familial 2 2015-09-21 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000444014 SCV000805802 likely benign not provided 2017-07-28 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001283689 SCV000885104 benign none provided 2020-08-07 criteria provided, single submitter clinical testing
Mendelics RCV000077475 SCV001138985 likely benign Breast-ovarian cancer, familial 2 2019-05-28 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center RCV001262844 SCV001440867 likely benign Familial cancer of breast 2019-01-01 criteria provided, single submitter clinical testing
Research and Development, ARUP Laboratories RCV001646968 SCV001854659 benign Breast-ovarian cancer, familial 2; Breast-ovarian cancer, familial 1; Hereditary breast and ovarian cancer syndrome 2020-01-20 criteria provided, single submitter curation
ITMI RCV000120308 SCV000084460 not provided not specified 2013-09-19 no assertion provided reference population
Sharing Clinical Reports Project (SCRP) RCV000077475 SCV000109273 benign Breast-ovarian cancer, familial 2 2012-09-11 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077475 SCV000145798 benign Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000120308 SCV000591723 benign not specified no assertion criteria provided clinical testing The c.978C>A, p.Ser326Arg variant has been previously identified in our laboratory in 4 patients with breast cancer as well as pancreatic cancer. It has also been reported in the literature in 11 of 11054 proband chromosomes in individuals with breast, ovarian and prostate cancer patients. The variant was not observed in any of the 206 control chromosomes tested (Edwards_2003, Spearman_2008, Caux-Moncoutier_2010, Sinilnikova_1999, Kote-Jarai_2011, Lee_2008, Martin_2001, Sinclair_2000, Shih_2000, Schroeder_2010, Schroeder, Rajasekaran_2008). These authors suggest that the variant be classified either as a variant of unknown significance or as a benign variant. It is listed in dbSNP database as coming from a "clinical source" (ID#:rs28897706) and in the exome variant server database with a global minor allele frequency (MAF) of 0.001 (1000 Genomes), increasing the likelihood that this is a low frequency benign variant. In addition, in two studies, the variant did not segregate with the disease (Shih_2000_11106241, Sinclair_2000_10728701). This residue is not conserved in mammals and the variant amino acid Arginine (Arg) is present in chicken and computational analyses (PolyPhen, SIFT, AlignGVGD) do not predict any effect on the protein function increasing the likelihood this variant does not have functional significance. The variant is observed in the UMD database in 5 of 30 individuals who had a second pathogenic mutation identified, again increasing the likelihood this variant is benign. The variant was also identified in In summary, based on the above information, this variant is classified as benign.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000077475 SCV000733221 benign Breast-ovarian cancer, familial 2 no assertion criteria provided clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000444014 SCV000778639 benign not provided 2017-10-25 no assertion criteria provided clinical testing
Clinical Genetics Laboratory, Department of Pathology,Netherlands Cancer Institute RCV000120308 SCV001905943 benign not specified no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000120308 SCV001959286 benign not specified no assertion criteria provided clinical testing

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