Submissions for variant NM_000059.4(BRCA2):c.10110G>A (p.Arg3370=) (rs28897762)

Total submissions: 26

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000112841	SCV000578017	benign	Breast-ovarian cancer, familial 2	2017-06-29	reviewed by expert panel	curation	Synonymous substitution variant, with low bioinformatic likelihood to alter mRNA splicing (splicing prior 0.02; http://priors.hci.utah.edu/PRIORS/) and frequency 0.002 (Non-Finnish European), 0.0018 (Finnish), 0.0014 (South Asian), derived from ExAC (2014-12-17).
Invitae	RCV000043713	SCV000071726	benign	Hereditary breast and ovarian cancer syndrome	2020-11-28	criteria provided, single submitter	clinical testing
GeneDx	RCV000168619	SCV000167427	benign	not specified	2013-12-16	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.
Michigan Medical Genetics Laboratories,University of Michigan	RCV000112841	SCV000196033	benign	Breast-ovarian cancer, familial 2	2014-11-03	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000162524	SCV000212919	likely benign	Hereditary cancer-predisposing syndrome	2014-06-27	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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.
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario	RCV000768612	SCV000219431	likely benign	Breast and/or ovarian cancer	2017-09-07	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV000260989	SCV000383809	uncertain significance	Fanconi anemia, complementation group D1	2018-01-12	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 did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina	RCV000043713	SCV000383810	likely benign	Hereditary breast and ovarian cancer syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000043713	SCV000494297	benign	Hereditary breast and ovarian cancer syndrome	2014-01-27	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000464865	SCV000541035	benign	Familial cancer of breast	2017-02-23	criteria provided, single submitter	clinical testing
Cancer Genetics and Genomics Laboratory,British Columbia Cancer Agency	RCV000168619	SCV000586994	benign	not specified	2017-04-18	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000168619	SCV000593734	likely benign	not specified	2017-05-11	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories	RCV001282333	SCV000602883	benign	none provided	2019-10-31	criteria provided, single submitter	clinical testing
Color Health, Inc	RCV000162524	SCV000683393	benign	Hereditary cancer-predisposing syndrome	2015-04-13	criteria provided, single submitter	clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics	RCV000168619	SCV000708489	likely benign	not specified	2017-05-15	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000112841	SCV000743530	benign	Breast-ovarian cancer, familial 2	2014-10-10	criteria provided, single submitter	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000112841	SCV000744795	benign	Breast-ovarian cancer, familial 2	2015-09-21	criteria provided, single submitter	clinical testing
PreventionGenetics,PreventionGenetics	RCV000656626	SCV000805641	likely benign	not provided	2017-05-15	criteria provided, single submitter	clinical testing
Mendelics	RCV000112841	SCV001139286	likely benign	Breast-ovarian cancer, familial 2	2019-05-28	criteria provided, single submitter	clinical testing
Breast Cancer Information Core (BIC) (BRCA2)	RCV000112841	SCV000145753	uncertain significance	Breast-ovarian cancer, familial 2	2000-06-12	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System	RCV000168619	SCV000592311	benign	not specified		no assertion criteria provided	clinical testing	BRCA2, c.10110G>A, p.Arg3370Arg, Predicted Benign. This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located near a splice junction, is listed in dbSNP (rs28897762) from a clinical source with an average heterozygosity and standard error of 0.004+/-0.047, and was also detected, with similar frequencies, in various ethnic mutation screening studies without any information to assess the significance of this variant (Bergthorsson_2001_11389159, Campos_2001_11843247, Diez_2003_12955716, Edwards_2003_12474142, Claes_2004_15026808, Infante_2006_16758124, Borg_2010_20104584, Stegel_2011_21232165). In addition, this variant is listed in the UMD mutation database to co-occur with a pathogenic mutation in BRCA1 (c.5330T>A/p.Tyr1769X), increasing the likelihood that p.Arg3370Arg is benign. Further, Myriad calls this a polymorphism (personal communication). In summary, based on the above information, the p.Arg3370Arg variant is predicted to be benign.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000112841	SCV000733343	benign	Breast-ovarian cancer, familial 2		no assertion criteria provided	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000656626	SCV000778728	likely benign	not provided	2017-05-15	no assertion criteria provided	clinical testing
True Health Diagnostics	RCV000162524	SCV000787914	likely benign	Hereditary cancer-predisposing syndrome	2017-10-10	no assertion criteria provided	clinical testing
Clinical Genetics Laboratory, Department of Pathology,Netherlands Cancer Institute	RCV000168619	SCV001905919	benign	not specified		no assertion criteria provided	clinical testing
Human Genetics - Radboudumc,Radboudumc	RCV000168619	SCV001955415	benign	not specified		no assertion criteria provided	clinical testing