Submissions for variant NM_000059.4(BRCA2):c.3264T>C (p.Pro1088=)

gnomAD frequency: 0.00793  dbSNP: rs36060526

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)	RCV000113152	SCV000245026	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 0.02642 (African), derived from 1000 genomes (2012-04-30).
Labcorp Genetics (formerly Invitae), Labcorp	RCV000044161	SCV000072174	benign	Hereditary breast ovarian cancer syndrome	2024-02-01	criteria provided, single submitter	clinical testing
Counsyl	RCV000113152	SCV000154082	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2014-03-14	criteria provided, single submitter	literature only
Eurofins Ntd Llc (ga)	RCV000152872	SCV000202283	benign	not specified	2015-04-29	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000162497	SCV000212884	benign	Hereditary cancer-predisposing syndrome	2014-09-16	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.
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000044161	SCV000257608	likely benign	Hereditary breast ovarian cancer syndrome	2015-04-14	criteria provided, single submitter	clinical testing
Michigan Medical Genetics Laboratories, University of Michigan	RCV000113152	SCV000267756	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2016-04-21	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000768626	SCV000324837	benign	Breast and/or ovarian cancer	2016-01-26	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000372410	SCV000383671	likely benign	Fanconi anemia complementation group D1	2018-01-19	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	RCV000113152	SCV000383672	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	2018-01-19	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	RCV000044161	SCV000494316	benign	Hereditary breast ovarian cancer syndrome	2014-04-11	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000474724	SCV000541036	benign	Familial cancer of breast	2017-02-23	criteria provided, single submitter	clinical testing
Cancer Genetics and Genomics Laboratory, British Columbia Cancer Agency	RCV000152872	SCV000586940	benign	not specified	2017-04-18	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000656595	SCV000602874	benign	not provided	2023-11-24	criteria provided, single submitter	clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000162497	SCV000679713	likely benign	Hereditary cancer-predisposing syndrome	2017-07-12	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000162497	SCV000683541	benign	Hereditary cancer-predisposing syndrome	2015-04-27	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000113152	SCV000743283	likely 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	RCV000113152	SCV000744437	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2015-09-21	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000152872	SCV000805690	benign	not specified	2017-04-13	criteria provided, single submitter	clinical testing
GeneDx	RCV000656595	SCV001911907	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 28324225)
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State	RCV000044161	SCV002026086	benign	Hereditary breast ovarian cancer syndrome	2022-04-19	criteria provided, single submitter	clinical testing
Genetics Program, Instituto Nacional de Cancer	RCV000044161	SCV002515263	benign	Hereditary breast ovarian cancer syndrome	2021-11-01	criteria provided, single submitter	research
Sema4, Sema4	RCV000162497	SCV002533779	benign	Hereditary cancer-predisposing syndrome	2020-06-25	criteria provided, single submitter	curation
Fulgent Genetics, Fulgent Genetics	RCV002490603	SCV002798671	likely 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	2022-04-13	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000113152	SCV004016840	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2023-07-07	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000656595	SCV004132978	benign	not provided	2023-01-01	criteria provided, single submitter	clinical testing	BRCA2: BP4, BP7, BS1, BS2
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000152872	SCV004242938	benign	not specified	2024-02-06	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000656595	SCV005236048	benign	not provided		criteria provided, single submitter	not provided
Breast Cancer Information Core (BIC) (BRCA2)	RCV000113152	SCV000146200	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2003-10-29	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001353464	SCV000591852	benign	Malignant tumor of breast		no assertion criteria provided	clinical testing	The p.Pro1088Pro variant is not expected to have clinical significance because it does not alter an amino acid residue and is not located near a splice junction. It is listed in the dbSNP database as coming from a "clinical source" (ID#: rs36060526) with a global minor allele frequency (MAF) of 0.006, increasing the likelihood that this is a low frequency benign variant. The variant has been reported in the literature in 9/7860 proband chromosomes of individuals with breast and prostate cancer; however, no control chromosomes were tested to establish the frequency of the variant in the general population (Borg_2010, Caux-Moncoutier_2011, Edwards_2003, Fackenthal_2005). The variant was also identified in the UMD database (x16), BIC database (x6), Exome Server database and the BOCs database. In the UMD database, this variant was identified in one individual with a second pathogenic variant in the BRCA2 gene (c.2808_2811delACAA, p.Ala938ProfsX21), increasing the likelihood that the p.Pro1088Pro variant is a benign alteration. In summary, based on the above information, this variant is classified as Benign.
Mayo Clinic Laboratories, Mayo Clinic	RCV000656595	SCV000778662	likely benign	not provided	2017-12-22	no assertion criteria provided	clinical testing
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000152872	SCV001905705	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000152872	SCV001954208	benign	not specified		no assertion criteria provided	clinical testing