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

dbSNP: rs1799966

Total submissions: 36

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, susceptibility to, 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 ovarian cancer syndrome	2024-02-01	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, susceptibility to, 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: seen in unaffected individuals, 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, susceptibility to, 1	2014-11-03	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000120260	SCV000202262	benign	not specified	2016-01-07	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000128996	SCV000292079	benign	Hereditary cancer-predisposing syndrome	2022-01-02	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000120260	SCV000311797	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000112410	SCV000403057	benign	Breast-ovarian cancer, familial, susceptibility to, 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 ovarian cancer syndrome	2013-10-08	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham 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	RCV002477059	SCV000575715	benign	Familial cancer of breast; Breast-ovarian cancer, familial, susceptibility to, 1; Pancreatic cancer, susceptibility to, 4; Fanconi anemia, complementation group S	2022-05-06	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	RCV000034753	SCV000602660	benign	not provided	2023-11-29	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, susceptibility to, 1	2014-10-09	criteria provided, single submitter	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000112410	SCV000744607	benign	Breast-ovarian cancer, familial, susceptibility to, 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
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State	RCV000119096	SCV002025927	benign	Hereditary breast ovarian cancer syndrome	2022-04-19	criteria provided, single submitter	clinical testing
GreenArray Genomic Research & Solutions of Accurate Diagnostic Private Limited	RCV000112410	SCV002097598	benign	Breast-ovarian cancer, familial, susceptibility to, 1		criteria provided, single submitter	clinical testing
Genetics Program, Instituto Nacional de Cancer	RCV000119096	SCV002515217	benign	Hereditary breast ovarian cancer syndrome	2021-11-01	criteria provided, single submitter	research
Sema4, Sema4	RCV000128996	SCV002537788	benign	Hereditary cancer-predisposing syndrome	2020-02-06	criteria provided, single submitter	curation
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000112410	SCV004016739	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2023-07-07	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000112410	SCV004817622	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2024-02-05	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, susceptibility to, 1		no assertion provided	clinical testing
Sharing Clinical Reports Project (SCRP)	RCV000112410	SCV000189345	benign	Breast-ovarian cancer, familial, susceptibility to, 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, susceptibility to, 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
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000120260	SCV001905915	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000120260	SCV001958274	benign	not specified		no assertion criteria provided	clinical testing