Submissions for variant NM_000059.4(BRCA2):c.4563A>G (p.Leu1521=) (rs206075)

Total submissions: 21

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000119245	SCV000245032	benign	Breast-ovarian cancer, familial 2	2015-01-12	reviewed by expert panel	curation	Class 1 not pathogenic based on frequency >1% in an outbred sampleset. Frequency 0.8902 (African), derived from 1000 genomes (2012-04-30).
Counsyl	RCV000119245	SCV000154035	benign	Breast-ovarian cancer, familial 2	2014-01-02	criteria provided, single submitter	literature only	High frequency in a 1kG or ESP population: 99.9 %.
GeneDx	RCV000152875	SCV000167365	benign	not specified	2014-12-09	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.
Ambry Genetics	RCV000132170	SCV000187248	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	RCV000119245	SCV000195985	benign	Breast-ovarian cancer, familial 2	2014-11-03	criteria provided, single submitter	clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics	RCV000152875	SCV000202287	benign	not specified	2015-10-13	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine	RCV000152875	SCV000268809	benign	not specified	2016-03-18	criteria provided, single submitter	clinical testing	This is a RefSeq error. The reference base (c.4563A) is the minor allele. This a llele (A) has been identified in 7.4% (758/10300) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs2060 75) and thus meets criteria to be classified as benign.
PreventionGenetics,PreventionGenetics	RCV000152875	SCV000301764	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV000119245	SCV000383698	benign	Breast-ovarian cancer, familial 2	2018-01-12	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Clinical Services Laboratory,Illumina	RCV000340564	SCV000383699	benign	Fanconi anemia, complementation group D1	2018-01-12	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Integrated Genetics/Laboratory Corporation of America	RCV000257902	SCV000494326	benign	Hereditary breast and ovarian cancer syndrome	2013-12-20	criteria provided, single submitter	clinical testing
Color Health, Inc	RCV000132170	SCV000537315	benign	Hereditary cancer-predisposing syndrome	2015-03-31	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000461053	SCV000541017	benign	Familial cancer of breast	2017-02-23	criteria provided, single submitter	clinical testing
Cancer Genetics and Genomics Laboratory,British Columbia Cancer Agency	RCV000152875	SCV000586951	benign	not specified	2017-04-18	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System	RCV000152875	SCV000591909	benign	not specified	2012-11-15	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories	RCV001282425	SCV000602737	benign	none provided	2020-09-01	criteria provided, single submitter	clinical testing
Invitae	RCV000257902	SCV000635377	benign	Hereditary breast and ovarian cancer syndrome	2019-12-31	criteria provided, single submitter	clinical testing
GeneKor MSA	RCV000152875	SCV000693637	benign	not specified	2017-11-01	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory,University Medical Center Utrecht	RCV000119245	SCV000743299	benign	Breast-ovarian cancer, familial 2	2014-10-10	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen	RCV000119245	SCV000733258	benign	Breast-ovarian cancer, familial 2		no assertion criteria provided	clinical testing
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic	RCV000656604	SCV000778675	benign	not provided	2016-11-28	no assertion criteria provided	clinical testing