Submissions for variant NM_000059.4(BRCA2):c.1786G>C (p.Asp596His) (rs56328701)

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)	RCV000083088	SCV001161606	benign	Breast-ovarian cancer, familial 2	2019-06-18	reviewed by expert panel	curation	IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 0.000066
Invitae	RCV000043882	SCV000071895	benign	Hereditary breast and ovarian cancer syndrome	2019-12-31	criteria provided, single submitter	clinical testing
Counsyl	RCV000083088	SCV000154038	likely benign	Breast-ovarian cancer, familial 2	2014-01-02	criteria provided, single submitter	literature only
Ambry Genetics	RCV000131138	SCV000186074	benign	Hereditary cancer-predisposing syndrome	2014-11-19	criteria provided, single submitter	clinical testing
Michigan Medical Genetics Laboratories,University of Michigan	RCV000083088	SCV000195962	benign	Breast-ovarian cancer, familial 2	2014-11-03	criteria provided, single submitter	clinical testing
GeneDx	RCV000120309	SCV000210568	benign	not specified	2015-02-19	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.
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario	RCV000768622	SCV000219305	benign	Breast and/or ovarian cancer	2016-03-03	criteria provided, single submitter	clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics	RCV000120309	SCV000224768	likely benign	not specified	2015-04-23	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV000292009	SCV000383635	likely benign	Fanconi anemia, complementation group D1	2018-08-30	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 Clinical Services Laboratory,Illumina	RCV000083088	SCV000383636	likely benign	Breast-ovarian cancer, familial 2	2018-08-30	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.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine	RCV000120309	SCV000538484	uncertain significance	not specified	2016-03-28	criteria provided, single submitter	clinical testing	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: ExAC: 0.1% (45/65250) European; ClinVar: 5 LB, 3 B
Cancer Genetics and Genomics Laboratory,British Columbia Cancer Agency	RCV000120309	SCV000586930	benign	not specified	2017-04-18	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System	RCV000120309	SCV000591765	benign	not specified	2014-08-07	criteria provided, single submitter	clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics	RCV000514736	SCV000610856	likely benign	not provided	2017-02-17	criteria provided, single submitter	clinical testing
Color	RCV000131138	SCV000683446	likely benign	Hereditary cancer-predisposing syndrome	2015-02-06	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory,University Medical Center Utrecht	RCV000083088	SCV000743263	benign	Breast-ovarian cancer, familial 2	2014-10-09	criteria provided, single submitter	clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center	RCV000083088	SCV000744414	benign	Breast-ovarian cancer, familial 2	2015-09-21	criteria provided, single submitter	clinical testing
PreventionGenetics,PreventionGenetics	RCV000120309	SCV000805655	benign	not specified	2017-07-31	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories	RCV000514736	SCV000885088	likely benign	not provided	2017-09-06	criteria provided, single submitter	clinical testing	The BRCA2 c.1786G>C;p.Asp596His variant has been listed as likely benign or of no clinical significance in at least two publications (Maxwell 2016, Minucci 2015). The variant is listed as likely benign by several sources in the ClinVar database (Variation ID: 51192). The variant is listed in the dbSNP variant database (rs56328701) with an allele frequency of 0.0385 percent (5/12995 alleles) in the Exome Variant Server and 0.03235 percent (88/272064 alleles) in the Genome Aggregation Consortium. The amino acid at this position is not well conserved across species and computational algorithms (AlignGVGD, SIFT, MutationTaster) predict this variant is tolerated. Considering available information, this variant is classified as likely benign. References: Maxwell KN et al. Evaluation of ACMG-Guideline-Based Variant Classification of Cancer Susceptibility and Non-Cancer-Associated Genes in Families Affected by Breast Cancer. Am J Hum Genet. 2016 May 5;98(5):801-17. Minucci A et al. Clinical impact on ovarian cancer patients of massive parallel sequencing for BRCA mutation detection: the experience at Gemelli hospital and a literature review. Expert Rev Mol Diagn. 2015;15(10):1383-403.
CeGaT Praxis fuer Humangenetik Tuebingen	RCV000514736	SCV000892063	likely benign	not provided	2018-06-01	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000514736	SCV001133693	likely benign	not provided	2019-01-17	criteria provided, single submitter	clinical testing
Mendelics	RCV000083088	SCV001139009	benign	Breast-ovarian cancer, familial 2	2019-05-28	criteria provided, single submitter	clinical testing
ITMI	RCV000120309	SCV000084461	not provided	not specified	2013-09-19	no assertion provided	reference population
Sharing Clinical Reports Project (SCRP)	RCV000083088	SCV000115162	benign	Breast-ovarian cancer, familial 2	2012-05-01	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA2)	RCV000083088	SCV000145933	not provided	Breast-ovarian cancer, familial 2		no assertion provided	clinical testing
CSER _CC_NCGL, University of Washington	RCV000148417	SCV000190116	likely benign	Neoplasm of the breast	2014-06-01	no assertion criteria provided	research
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen	RCV000083088	SCV000733233	benign	Breast-ovarian cancer, familial 2		no assertion criteria provided	clinical testing
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic	RCV000514736	SCV000778646	benign	not provided	2017-04-20	no assertion criteria provided	clinical testing