ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.4837A>G (p.Ser1613Gly) (rs1799966)

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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) RCV000112410 SCV000244369 benign Breast-ovarian cancer, familial 1 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 = 0.00000000000309. Also class 1 based on frequency >1% in an outbred sampleset. Frequency 0.3322 (Asian), 0.2195 (African), 0.3615 (European), derived from 1000 genomes (2012-04-30).
Invitae RCV000119096 SCV000076685 benign Hereditary breast and ovarian cancer syndrome 2020-12-01 criteria provided, single submitter clinical testing
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000048672 SCV000148891 benign Familial cancer of breast 2020-05-03 criteria provided, single submitter clinical testing
Counsyl RCV000112410 SCV000154004 benign Breast-ovarian cancer, familial 1 2014-01-02 criteria provided, single submitter literature only High frequency in a 1kG or ESP population: 32.7 %.
Ambry Genetics RCV000128996 SCV000172891 benign Hereditary cancer-predisposing syndrome 2014-08-19 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.
Michigan Medical Genetics Laboratories,University of Michigan RCV000112410 SCV000195933 benign Breast-ovarian cancer, familial 1 2014-11-03 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000120260 SCV000202262 benign not specified 2016-01-07 criteria provided, single submitter clinical testing
Color Health, Inc RCV000128996 SCV000292079 benign Hereditary cancer-predisposing syndrome 2014-11-04 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000120260 SCV000311797 benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000112410 SCV000403057 benign Breast-ovarian cancer, familial 1 2018-03-06 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000119096 SCV000494328 benign Hereditary breast and ovarian cancer syndrome 2013-10-08 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000120260 SCV000538430 benign not specified 2016-03-29 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: Frequency
Baylor Genetics RCV000048672 SCV000540959 benign Familial cancer of breast 2017-02-23 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000112410 SCV000575715 likely benign Breast-ovarian cancer, familial 1 2015-12-17 criteria provided, single submitter clinical testing
Cancer Genetics and Genomics Laboratory,British Columbia Cancer Agency RCV000120260 SCV000586901 benign not specified 2017-04-18 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001282984 SCV000602660 benign none provided 2020-09-01 criteria provided, single submitter clinical testing
GeneKor MSA RCV000120260 SCV000693617 benign not specified 2017-11-01 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000112410 SCV000743387 benign Breast-ovarian cancer, familial 1 2014-10-09 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000112410 SCV000744607 benign Breast-ovarian cancer, familial 1 2015-09-21 criteria provided, single submitter clinical testing
Center for Medical Genomics, Faculty of Medicine Ramathibodi Hospital, Mahidol University,Faculty of Medicine Ramathibodi Hospital, Mahidol University RCV000767866 SCV000897720 benign Breast carcinoma 2019-04-03 criteria provided, single submitter clinical testing
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034753 SCV000043156 no known pathogenicity not provided 2012-07-13 no assertion criteria provided research Converted during submission to Benign.
ITMI RCV000120260 SCV000084412 not provided not specified 2013-09-19 no assertion provided reference population
Breast Cancer Information Core (BIC) (BRCA1) RCV000112410 SCV000145193 not provided Breast-ovarian cancer, familial 1 no assertion provided clinical testing
Sharing Clinical Reports Project (SCRP) RCV000112410 SCV000189345 benign Breast-ovarian cancer, familial 1 2011-03-22 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000120260 SCV000591541 benign not specified no assertion criteria provided clinical testing The p.Ser1613Gly variant was identified extensively in the literature from individuals or families with hereditary breast and ovarian cancers, and also control chromosomes from healthy individuals (Shattuck-Eidens 1997, Tavtigian 2006, Tommasi 2008, Phelan 2005, McKean-Cowdin 2005, Johnson 2007, Ho-Gay 2000, Greenman 1998, Forat-Yazdi 2015, Diez 2003, Abkevich 2004, Carvalho 2007). Most of the studies have concluded the p.Ser1613Gly variant benign or a polymorphism. The variant was also identified in our laboratory and in dbSNP (ID: rs1799966) with benign/other allele; in the 1000 Genomes Project in 1782 of 5000 chromosomes (frequency: 0.3558); in HapMap-CEU in 151 of 220 chromosomes (frequency: 0.686363); HapMap-YRI in 187 of 226 chromosomes (frequency: 0.8274333); HapMap-MKK in 224 of 286 chromosomes (frequency: 0.78321677). In Exome Variant Server project the variant was identified in 2809 of 8600 (freq: 0.326627) European American and in 1069 of 4406 (freq: 0.2426) African American alleles. In the Exome Aggregation Consortium (ExAC) database (released Oct 20th, 2014) the variant was identified in 42424 of 121360 chromosomes, with 7852 homozygotes (frequency: 0.3496) from a population of South Asians, European (Non-Finnish), East Asian, African, Latino, European (Finnish) and other individuals. The variant was identified in GeneInsight COGR, Clinvar (8 of 10 submitters classified as benign), Clinvitae, COSMIC, BRCA Share-UMD (co-occurred with BRCA1 and BRCA2 pathogenic variants), BIC, ARUP, LOVD and Fanconi’s Anemia LOVD databases. The p.Ser1613 residue is not conserved in mammals and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein. In summary, based on the above information, this variant meets our laboratory's criteria to be classified as benign.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000112410 SCV000733604 benign Breast-ovarian cancer, familial 1 no assertion criteria provided clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000034753 SCV000778736 benign not provided 2016-11-28 no assertion criteria provided clinical testing
Center of Medical Genetics and Primary Health Care RCV001269364 SCV001448709 benign Malignant tumor of breast no assertion criteria provided clinical testing

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