Submissions for variant NM_000059.4(BRCA2):c.4068G>A (p.Leu1356=)

gnomAD frequency: 0.00295  dbSNP: rs28897724

Total submissions: 40

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000113269	SCV000578007	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 0.0047 (Non-Finnish European), 0.0023 (Finnish), 0.0029 (Admixed American/Latino), derived from ExAC (2014-12-17).
Invitae	RCV000044340	SCV000072353	benign	Hereditary breast ovarian cancer syndrome	2024-02-01	criteria provided, single submitter	clinical testing
Counsyl	RCV000113269	SCV000154069	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	2014-02-07	criteria provided, single submitter	literature only
Michigan Medical Genetics Laboratories, University of Michigan	RCV000113269	SCV000195979	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2014-11-03	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000162367	SCV000212675	benign	Hereditary cancer-predisposing syndrome	2014-07-15	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	RCV000768629	SCV000219334	benign	Breast and/or ovarian cancer	2019-04-23	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000168569	SCV000225166	benign	not specified	2014-08-22	criteria provided, single submitter	clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000044340	SCV000267843	likely benign	Hereditary breast ovarian cancer syndrome	2016-04-25	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000385860	SCV000383691	likely benign	Fanconi anemia complementation group D1	2018-05-15	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.
Illumina Laboratory Services, Illumina	RCV000113269	SCV000383692	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	2018-05-15	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000044340	SCV000494322	benign	Hereditary breast ovarian cancer syndrome	2014-03-17	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000113269	SCV000575765	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2016-02-25	criteria provided, single submitter	clinical testing
Cancer Genetics and Genomics Laboratory, British Columbia Cancer Agency	RCV000168569	SCV000586947	benign	not specified	2017-04-18	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000168569	SCV000593714	benign	not specified	2019-06-10	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000513194	SCV000602805	benign	not provided	2023-11-17	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000513194	SCV000608679	likely benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	BRCA2: BP4, BP7, BS2
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000162367	SCV000679716	likely benign	Hereditary cancer-predisposing syndrome	2017-07-12	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000162367	SCV000683598	benign	Hereditary cancer-predisposing syndrome	2015-04-15	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000113269	SCV000743294	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	RCV000113269	SCV000744450	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	2015-09-21	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000168569	SCV000805703	benign	not specified	2016-11-30	criteria provided, single submitter	clinical testing
Mendelics	RCV000113269	SCV001139081	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	2019-05-28	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV001262741	SCV001440719	likely benign	Familial cancer of breast	2019-01-01	criteria provided, single submitter	clinical testing
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State	RCV000044340	SCV002026098	benign	Hereditary breast ovarian cancer syndrome	2021-11-16	criteria provided, single submitter	clinical testing
Genetics Program, Instituto Nacional de Cancer	RCV000044340	SCV002515269	benign	Hereditary breast ovarian cancer syndrome	2021-11-01	criteria provided, single submitter	research
Sema4, Sema4	RCV000162367	SCV002533844	benign	Hereditary cancer-predisposing syndrome	2021-03-25	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000168569	SCV002550332	benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
Genetics and Molecular Pathology, SA Pathology	RCV000113269	SCV002761726	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2020-02-17	criteria provided, single submitter	clinical testing	The BRCA2 c.4068G>A variant is classified as Benign (BA1) This BRCA2 c.4068G>A variant is synonymous (silent). The frequency of this variant in population databases is higher than expected for this disorder indicating this variant is a benign polymorphism (BA1). Population frequency of .29% for this variant greater than expected for pathogenic BRCA2 variants (expected to be 0.45% for all BRCA2 pathogenic variants). ENIGMA BRCA1/2 Classification Criteria (2017-06-29): benign
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000113269	SCV004016823	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2023-07-07	criteria provided, single submitter	clinical testing
Breast Cancer Information Core (BIC) (BRCA2)	RCV000113269	SCV000146368	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2004-02-20	no assertion criteria provided	clinical testing
Sharing Clinical Reports Project (SCRP)	RCV000113269	SCV000189305	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2011-03-14	no assertion criteria provided	clinical testing
Department of Medical Genetics, University Hospital of North Norway	RCV000113269	SCV000301447	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2016-05-01	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001353901	SCV000591887	benign	Malignant tumor of breast		no assertion criteria provided	clinical testing	The p.Leu1356Leu variant has been reported in the literature in 29/16512 proband chromosomes and 0/80 control chromosomes. However, an insufficient number of controls were typed to establish the variants' allele frequency in the general population (Edwards 2003, Haffty 2006, Infante 2006, Stagel 2011, Van der Hout 2006, Yang 2009). This 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 reported in dbSNP (ID#:rs28897724) with a global allele frequency of 0.001 (1000 genomes) increasing the likelihood this variant is benign. In addition, this variant is reported by Myriad Genetics as benign as of Oct 2008 (personal communication). In summary, this variant meets our laboratories' criteria for a benign variant.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000113269	SCV000733252	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2		no assertion criteria provided	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000513194	SCV000778670	benign	not provided	2017-08-22	no assertion criteria provided	clinical testing
True Health Diagnostics	RCV000162367	SCV000805242	likely benign	Hereditary cancer-predisposing syndrome	2018-05-03	no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000513194	SCV001798902	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000168569	SCV001905840	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000168569	SCV001959526	benign	not specified		no assertion criteria provided	clinical testing
BRCAlab, Lund University	RCV000113269	SCV004243619	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2020-03-02	no assertion criteria provided	clinical testing