Submissions for variant NM_000059.3(BRCA2):c.7052C>G (p.Ala2351Gly) (rs80358932)

Total submissions: 17

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000587020	SCV000073143	benign	not provided	2019-02-12	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	In silico models in agreement (benign);Other data supporting benign classification;No disease association in small case-control study
GeneDx	RCV000120352	SCV000210642	likely benign	not specified	2017-10-23	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Illumina Clinical Services Laboratory,Illumina	RCV000343881	SCV000383756	likely benign	Fanconi anemia	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV000167842	SCV000383757	likely benign	Hereditary breast and ovarian cancer syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System	RCV000120352	SCV000592095	benign	not specified	2012-11-15	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000120352	SCV000602839	benign	not specified	2016-12-05	criteria provided, single submitter	clinical testing
Integrated Genetics/Laboratory Corporation of America	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 2	2014-10-09	criteria provided, single submitter	clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center	RCV000031663	SCV000744508	likely benign	Breast-ovarian cancer, familial 2	2015-09-21	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000587020	SCV000889124	benign	not provided	2019-05-17	criteria provided, single submitter	clinical testing
Color	RCV000131678	SCV000910634	benign	Hereditary cancer-predisposing syndrome	2015-12-02	criteria provided, single submitter	clinical testing
Sharing Clinical Reports Project (SCRP)	RCV000031663	SCV000054270	benign	Breast-ovarian cancer, familial 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 2	2002-05-29	no assertion criteria provided	clinical testing
Pathway Genomics	RCV000031663	SCV000189909	likely benign	Breast-ovarian cancer, familial 2	2014-07-24	no assertion criteria provided	clinical testing
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic	RCV000587020	SCV000778702	likely benign	not provided	2017-02-20	no assertion criteria provided	clinical testing