Submissions for variant NM_000059.4(BRCA2):c.7017G>C (p.Lys2339Asn) (rs45574331)

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)	RCV000113692	SCV000245106	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 0.02642 (African), derived from 1000 genomes (2012-04-30).
Invitae	RCV000167851	SCV000073134	benign	Hereditary breast and ovarian cancer syndrome	2020-12-08	criteria provided, single submitter	clinical testing
Counsyl	RCV000113692	SCV000154081	benign	Breast-ovarian cancer, familial 2	2014-03-18	criteria provided, single submitter	literature only
Ambry Genetics	RCV000128918	SCV000172785	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.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics	RCV000120355	SCV000202294	benign	not specified	2013-12-06	criteria provided, single submitter	clinical testing
Pathway Genomics	RCV000113692	SCV000223770	benign	Breast-ovarian cancer, familial 2	2014-10-30	criteria provided, single submitter	clinical testing
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia	RCV000167851	SCV000257617	likely benign	Hereditary breast and ovarian cancer syndrome	2015-04-14	criteria provided, single submitter	clinical testing
Michigan Medical Genetics Laboratories,University of Michigan	RCV000113692	SCV000267805	benign	Breast-ovarian cancer, familial 2	2016-04-21	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario	RCV000768605	SCV000324839	benign	Breast and/or ovarian cancer	2016-01-26	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV000383466	SCV000383754	likely benign	Fanconi anemia, complementation group D1	2018-01-19	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	RCV000113692	SCV000383755	likely benign	Breast-ovarian cancer, familial 2	2018-01-19	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000167851	SCV000494340	benign	Hereditary breast and ovarian cancer syndrome	2014-04-15	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine	RCV000120355	SCV000538462	benign	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: 2.7% (262/9870) African chromosomes
Baylor Genetics	RCV000465613	SCV000541038	benign	Familial cancer of breast	2017-02-23	criteria provided, single submitter	clinical testing
Cancer Genetics and Genomics Laboratory,British Columbia Cancer Agency	RCV000120355	SCV000586971	benign	not specified	2017-04-18	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories	RCV001282541	SCV000602876	benign	none provided	2020-06-24	criteria provided, single submitter	clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics	RCV000514662	SCV000610790	benign	not provided	2017-05-30	criteria provided, single submitter	clinical testing
Color Health, Inc	RCV000128918	SCV000683843	benign	Hereditary cancer-predisposing syndrome	2015-03-05	criteria provided, single submitter	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000113692	SCV000744507	benign	Breast-ovarian cancer, familial 2	2015-09-21	criteria provided, single submitter	clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000128918	SCV000747801	likely benign	Hereditary cancer-predisposing syndrome	2018-01-16	criteria provided, single submitter	clinical testing
PreventionGenetics,PreventionGenetics	RCV000120355	SCV000805755	benign	not specified	2017-04-13	criteria provided, single submitter	clinical testing
ITMI	RCV000120355	SCV000084507	not provided	not specified	2013-09-19	no assertion provided	reference population
Breast Cancer Information Core (BIC) (BRCA2)	RCV000113692	SCV000147001	uncertain significance	Breast-ovarian cancer, familial 2	2002-05-29	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System	RCV001353904	SCV000592091	benign	Malignant tumor of breast		no assertion criteria provided	clinical testing	The p.Lys2339Asn variant has been previously reported in the literature in 10/8236 proband chromosomes, and in none of the 132 control chromosomes tested (Capanu_2011_21520273, Gao_2000_11030417, Kote-Jarai_2011_21952622, Nanda_2005_16234499). It is listed in the dbSNP database as coming from a "clinical source" (ID#: rs45574331) with a MAF score of 0.006 (1000 Genomes). The variant was identified at high frequency >2.6% in African population from ExAC increasing likelihood this is a common benign polymorphism. The variant was also identified in the UMD (x19), BIC, Exome Server and the BOCs databases. In addition, in the UMD database, the p.Lys2339Asn variant was found to co-occur with a pathogenic mutation in BRCA1, c.2709_2710delTG (p.Cys903X), increasing the likelihood that the variant is a benign alteration. This residue is not conserved in mammals and computational analyses (SIFT, AlignGVGD) do not suggest a high likelihood of impact to the protein. However, this information is not predictive enough to rule out pathogenicity. In summary, based on the above information, we cannot determine the clinical significance of this variant with certainty at this time, although we would lean towards a more benign role for this variant. In summary, this variant is classified as Benign.
Mayo Clinic Laboratories, Mayo Clinic	RCV000514662	SCV000778701	benign	not provided	2017-12-23	no assertion criteria provided	clinical testing
Clinical Genetics Laboratory, Department of Pathology,Netherlands Cancer Institute	RCV000120355	SCV001906102	benign	not specified		no assertion criteria provided	clinical testing
Human Genetics - Radboudumc,Radboudumc	RCV000120355	SCV001956315	benign	not specified		no assertion criteria provided	clinical testing