Submissions for variant NM_000059.4(BRCA2):c.3516G>A (p.Ser1172=)

gnomAD frequency: 0.00228  dbSNP: rs1799952

Total submissions: 33

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000113188	SCV000578026	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2017-06-29	reviewed by expert panel	curation	Synonymous substitution variant, with low bioinformatic likelihood to alter mRNA splicing (splicing prior 0.02; http://priors.hci.utah.edu/PRIORS/) and frequency 0.0049 (Non-Finnish European), 0.003 (Finnish), 0.0012 (South Asian), derived from ExAC (2014-12-17).
Invitae	RCV000044214	SCV000072227	benign	Hereditary breast ovarian cancer syndrome	2024-02-01	criteria provided, single submitter	clinical testing
Counsyl	RCV000113188	SCV000154043	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	2014-01-02	criteria provided, single submitter	literature only
Ambry Genetics	RCV000162494	SCV000212877	likely benign	Hereditary cancer-predisposing syndrome	2014-06-13	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000768627	SCV000219327	likely benign	Breast and/or ovarian cancer	2016-06-01	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000168565	SCV000225173	benign	not specified	2014-12-02	criteria provided, single submitter	clinical testing
Michigan Medical Genetics Laboratories, University of Michigan	RCV000113188	SCV000267760	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2016-04-21	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000113188	SCV000383685	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	2018-01-13	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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV000268403	SCV000383686	likely benign	Fanconi anemia complementation group D1	2018-01-13	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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000044214	SCV000494318	benign	Hereditary breast ovarian cancer syndrome	2014-04-22	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002477145	SCV000575761	benign	Familial cancer of breast; Breast-ovarian cancer, familial, susceptibility to, 2; Fanconi anemia complementation group D1; Medulloblastoma; Wilms tumor 1; Malignant tumor of prostate; Pancreatic cancer, susceptibility to, 2; Glioma susceptibility 3	2022-04-26	criteria provided, single submitter	clinical testing
Cancer Genetics and Genomics Laboratory, British Columbia Cancer Agency	RCV000168565	SCV000586943	benign	not specified	2017-04-18	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000168565	SCV000593712	benign	not specified	2021-06-15	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000656597	SCV000602815	benign	not provided	2023-08-28	criteria provided, single submitter	clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000162494	SCV000679714	likely benign	Hereditary cancer-predisposing syndrome	2017-07-12	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000162494	SCV000683565	benign	Hereditary cancer-predisposing syndrome	2015-04-07	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000113188	SCV000743286	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	2014-10-10	criteria provided, single submitter	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000113188	SCV000744440	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2015-09-21	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000168565	SCV000805694	benign	not specified	2017-07-11	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000656597	SCV001148980	likely benign	not provided	2024-07-01	criteria provided, single submitter	clinical testing	BRCA2: BP4, BP7
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000168565	SCV001469418	benign	not specified	2020-06-14	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000162494	SCV002533805	benign	Hereditary cancer-predisposing syndrome	2020-02-24	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000168565	SCV002550323	benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
Genetics and Molecular Pathology, SA Pathology	RCV000113188	SCV002556530	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2021-05-28	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000113188	SCV004016836	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2023-07-07	criteria provided, single submitter	clinical testing
Breast Cancer Information Core (BIC) (BRCA2)	RCV000113188	SCV000146252	not provided	Breast-ovarian cancer, familial, susceptibility to, 2		no assertion provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000168565	SCV000591866	benign	not specified		no assertion criteria provided	clinical testing	The p.Ser1172Ser variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located near a splice junction, and is listed in dbSNP (rs1799952) with a heterozygosity of 0.007+/-0.058. This variant has been observed at least 10x in the presence of a second pathogenic variant in the UMD database, suggesting it does not have clinical significance. In addition, Myriad classifies this variant as a polymorphism.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000113188	SCV000733246	benign	Breast-ovarian cancer, familial, susceptibility to, 2		no assertion criteria provided	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000656597	SCV000778664	likely benign	not provided	2017-07-21	no assertion criteria provided	clinical testing
True Health Diagnostics	RCV000162494	SCV000787928	likely benign	Hereditary cancer-predisposing syndrome	2017-12-01	no assertion criteria provided	clinical testing
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000168565	SCV001905777	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000168565	SCV001956861	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000656597	SCV002036125	likely benign	not provided		no assertion criteria provided	clinical testing