Submissions for variant NM_000059.4(BRCA2):c.7052C>G (p.Ala2351Gly)

gnomAD frequency: 0.00005  dbSNP: rs80358932

Total submissions: 24

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000167842	SCV000073143	benign	Hereditary breast ovarian cancer syndrome	2024-01-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000131678	SCV000186714	likely benign	Hereditary cancer-predisposing syndrome	2018-08-14	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.
GeneDx	RCV000587020	SCV000210642	likely benign	not provided	2020-11-25	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 21990134, 20104584, 21990165, 28664449, 27658390, 24728327, 16949048, 21218378, 18824701, 17100994, 18006916, 21520273, 28222693, 27124784, 27150160, 21120943, 18779604, 26435481, 29731985, 28678401, 27907908, 29020732, 30415210, 28111427, 30093976, 31131967, 31825140)
Illumina Laboratory Services, Illumina	RCV000343881	SCV000383756	likely benign	Fanconi anemia complementation group D1	2017-04-27	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	RCV000031663	SCV000383757	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	2017-04-27	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000120352	SCV000602839	benign	not specified	2016-12-05	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000587020	SCV000695031	benign	not provided	2016-03-21	criteria provided, single submitter	clinical testing	Variant Summary: The BRCA2 variant of interest causes a missense change involving a non-conserved nucleotide with 2/4 in silico programs predicting a "benign" outcome (SNPs&Go not captured here due to low reliability index), although these predictions have yet to be functionally assessed. The variant of interest was observed in a large, broad control population, ExAC with an allele frequency of 16/120976 (1/7561), predominantly in the East Asian cohort, 15/8648 (1/577), which significantly exceeds the maximal expected allele frequency for a pathogenic BRCA2 variant of 1/1333, therefore suggesting the variant of interest is a common polymorphism found in population(s) of East Asian origin. The variant of interest has been reported in affected individuals via publicatins, predominantly in those of Asian decent, although limited information is provided (i.e. lack of co-occurrence and co-segregation information being provided). The variant of interest has been reported by multiple reputable databases/clinical laboratories as "likely benign/benign." Additionally, the BIC database reports one individual with a pathogenic BRCA2 co-occurrence, c.1103C>A (p.Ser368Ter). Therefore, taking all lines of evidence into consideration, the variant of interest is classified as benign.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000031663	SCV000743328	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	2014-10-09	criteria provided, single submitter	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000031663	SCV000744508	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	2015-09-21	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000587020	SCV000889124	benign	not provided	2023-07-31	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000131678	SCV000910634	benign	Hereditary cancer-predisposing syndrome	2015-12-02	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001798052	SCV002043422	likely benign	Breast and/or ovarian cancer	2021-04-19	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000120352	SCV002070533	likely benign	not specified	2019-08-27	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000131678	SCV002531832	likely benign	Hereditary cancer-predisposing syndrome	2021-07-13	criteria provided, single submitter	curation
Sharing Clinical Reports Project (SCRP)	RCV000031663	SCV000054270	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2012-05-01	no assertion criteria provided	clinical testing
ITMI	RCV000120352	SCV000084504	not provided	not specified	2013-09-19	no assertion provided	reference population
Breast Cancer Information Core (BIC) (BRCA2)	RCV000031663	SCV000147009	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2002-05-29	no assertion criteria provided	clinical testing
Pathway Genomics	RCV000031663	SCV000189909	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	2014-07-24	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001353781	SCV000592095	benign	Malignant tumor of breast		no assertion criteria provided	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000587020	SCV000778702	likely benign	not provided	2017-02-20	no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000587020	SCV001800806	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000587020	SCV001906120	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000587020	SCV001955948	likely benign	not provided		no assertion criteria provided	clinical testing
Center for Precision Medicine, Meizhou People's Hospital	RCV002250490	SCV002520826	likely benign	Familial cancer of breast		no assertion criteria provided	literature only