Submissions for variant NM_000059.4(BRCA2):c.-11C>T

gnomAD frequency: 0.00539  dbSNP: rs76874770

Total submissions: 28

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000113002	SCV000244918	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2015-01-12	reviewed by expert panel	curation	Class 1 not pathogenic based on frequency >1% in an outbred sampleset. Frequency 0.02236 (African), derived from 1000 genomes (2012-04-30).
Ambry Genetics	RCV000131010	SCV000185936	benign	Hereditary cancer-predisposing syndrome	2014-07-29	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	RCV000113002	SCV000195943	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2014-11-03	criteria provided, single submitter	clinical testing
Counsyl	RCV000113002	SCV000220306	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2014-05-12	criteria provided, single submitter	literature only
Eurofins Ntd Llc (ga)	RCV000175515	SCV000227007	benign	not specified	2014-07-16	criteria provided, single submitter	clinical testing
Invitae	RCV000205927	SCV000260705	benign	Hereditary breast ovarian cancer syndrome	2024-02-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000370664	SCV000383599	likely benign	Fanconi anemia complementation group D1	2018-11-01	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	RCV000113002	SCV000383600	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	2018-11-01	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000205927	SCV000494355	benign	Hereditary breast ovarian cancer syndrome	2014-04-15	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000175515	SCV000593696	likely benign	not specified	2016-03-10	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001705819	SCV000602859	benign	not provided	2022-04-04	criteria provided, single submitter	clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000131010	SCV000679705	likely benign	Hereditary cancer-predisposing syndrome	2017-07-12	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000131010	SCV000683383	benign	Hereditary cancer-predisposing syndrome	2022-01-02	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000113002	SCV000743233	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2017-07-28	criteria provided, single submitter	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000113002	SCV000744376	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2015-09-21	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000175515	SCV000805638	benign	not specified	2016-11-22	criteria provided, single submitter	clinical testing
GeneDx	RCV001705819	SCV001885120	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State	RCV000205927	SCV002026059	benign	Hereditary breast ovarian cancer syndrome	2022-04-19	criteria provided, single submitter	clinical testing
Genetics Program, Instituto Nacional de Cancer	RCV000205927	SCV002515236	benign	Hereditary breast ovarian cancer syndrome	2021-11-01	criteria provided, single submitter	research
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003149775	SCV003838811	benign	Breast and/or ovarian cancer	2021-10-29	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000113002	SCV004016860	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2023-07-07	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000175515	SCV004242594	benign	not specified	2024-02-06	criteria provided, single submitter	clinical testing
Breast Cancer Information Core (BIC) (BRCA2)	RCV000113002	SCV000145987	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2002-05-29	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001353870	SCV000591651	benign	Malignant tumor of breast		no assertion criteria provided	clinical testing	The c.-11C>T variant was identified in the literature in 8/5532 proband chromosomes in individuals with breast cancer, and was absent in 148 control chromosomes evaluated (Borg_2010_20104584, Diez_2003_12955716, Fackenthal_2005_15744044). The variant is located in the 5’ untranslated region (promoter) and is not part of a splicing consensus sequence. It is possible that this variant may influence the binding of transcription factors and expression or processing of the BRCA2 mRNA transcript. The c.-11C>T variant was also identified in dbSNP (ID#:rs76874770), the BIC database (48X with unknown clinical significance), and in UMD (22X as an unclassified variant). In the UMD database, the variant was observed to co-occur with another BRCA2 pathogenic mutation (c.6159delT (p.Ala2054LeufsX16)) increasing the likelihood that this variant may not have clinical significance. The variant was listed in the 1000 Genomes Project with a frequency 0.005, and in the NHLBI Exome Sequencing Project with a frequency of 0.02 in African American alleles, increasing the likelihood that this may be a benign variant in certain populations of origin. 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	RCV000113002	SCV000733205	benign	Breast-ovarian cancer, familial, susceptibility to, 2		no assertion criteria provided	clinical testing
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000175515	SCV001905906	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000175515	SCV001958715	benign	not specified		no assertion criteria provided	clinical testing
BRCAlab, Lund University	RCV000113002	SCV004243814	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2020-03-02	no assertion criteria provided	clinical testing