Submissions for variant NM_000059.4(BRCA2):c.1151C>T (p.Ser384Phe) (rs41293475)

Total submissions: 27

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000112886	SCV000244418	benign	Breast-ovarian cancer, familial 2	2015-08-10	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 = 0.000424
Invitae	RCV000043747	SCV000071760	benign	Hereditary breast and ovarian cancer syndrome	2019-12-31	criteria provided, single submitter	clinical testing
GeneDx	RCV000120306	SCV000108596	benign	not specified	2017-07-25	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.
Counsyl	RCV000112886	SCV000154036	likely benign	Breast-ovarian cancer, familial 2	2014-01-02	criteria provided, single submitter	literature only
Ambry Genetics	RCV000162684	SCV000213138	benign	Hereditary cancer-predisposing syndrome	2014-11-19	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	RCV000112886	SCV000267742	likely benign	Breast-ovarian cancer, familial 2	2016-04-21	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV000112886	SCV000383628	likely benign	Breast-ovarian cancer, familial 2	2018-03-06	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine	RCV000120306	SCV000538482	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: Multiple publications classify as VUS/not pathogenic; ExAC: 0.1% (69/66720) European chromosomes
Cancer Genetics and Genomics Laboratory,British Columbia Cancer Agency	RCV000120306	SCV000586925	benign	not specified	2017-04-18	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System	RCV000120306	SCV000591730	benign	not specified	2013-01-04	criteria provided, single submitter	clinical testing
Genetic Services Laboratory,University of Chicago	RCV000120306	SCV000593701	likely benign	not specified	2015-08-31	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories	RCV000034428	SCV000602838	benign	not provided	2017-09-01	criteria provided, single submitter	clinical testing
Color Health, Inc	RCV000162684	SCV000683404	likely benign	Hereditary cancer-predisposing syndrome	2015-02-16	criteria provided, single submitter	clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen	RCV000034428	SCV000692768	likely benign	not provided	2020-03-01	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory,University Medical Center Utrecht	RCV000112886	SCV000743256	benign	Breast-ovarian cancer, familial 2	2014-10-09	criteria provided, single submitter	clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center	RCV000112886	SCV000744403	benign	Breast-ovarian cancer, familial 2	2015-09-21	criteria provided, single submitter	clinical testing
PreventionGenetics,PreventionGenetics	RCV000034428	SCV000805647	likely benign	not provided	2018-01-17	criteria provided, single submitter	clinical testing
Mendelics	RCV000112886	SCV001138990	likely benign	Breast-ovarian cancer, familial 2	2019-05-28	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV001112104	SCV001269725	uncertain significance	Fanconi anemia, complementation group D1	2018-03-06	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Biesecker Lab/Clinical Genomics Section,National Institutes of Health	RCV000034428	SCV000043196	probably not pathogenic	not provided	2012-07-13	no assertion criteria provided	research	Converted during submission to Likely benign.
ITMI	RCV000120306	SCV000084458	not provided	not specified	2013-09-19	no assertion provided	reference population
Breast Cancer Information Core (BIC) (BRCA2)	RCV000112886	SCV000145823	benign	Breast-ovarian cancer, familial 2	2002-05-29	no assertion criteria provided	clinical testing
CSER _CC_NCGL, University of Washington	RCV000148428	SCV000190127	uncertain significance	Breast neoplasm	2014-06-01	no assertion criteria provided	research
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto	RCV000120306	SCV000587580	benign	not specified	2014-01-31	no assertion criteria provided	research
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen	RCV000112886	SCV000733224	benign	Breast-ovarian cancer, familial 2		no assertion criteria provided	clinical testing
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic	RCV000034428	SCV000778641	likely benign	not provided	2016-12-08	no assertion criteria provided	clinical testing
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research	RCV000735441	SCV000863577	uncertain significance	Breast and/or ovarian cancer	2001-08-21	no assertion criteria provided	clinical testing