Submissions for variant NM_007294.4(BRCA1):c.2733A>G (p.Gly911=)

gnomAD frequency: 0.00066  dbSNP: rs1800740

Total submissions: 25

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000111927	SCV000578175	likely benign	Breast-ovarian cancer, familial, susceptibility to, 1	2017-06-29	reviewed by expert panel	curation	Synonymous substitution variant, with low bioinformatic likelihood to result in a splicing aberration (Splicing prior probability 0.02; http://priors.hci.utah.edu/PRIORS/).
Invitae	RCV000047951	SCV000075964	benign	Hereditary breast ovarian cancer syndrome	2024-01-31	criteria provided, single submitter	clinical testing
Counsyl	RCV000111927	SCV000154016	likely benign	Breast-ovarian cancer, familial, susceptibility to, 1	2014-01-25	criteria provided, single submitter	literature only
Ambry Genetics	RCV000162536	SCV000212937	likely benign	Hereditary cancer-predisposing syndrome	2014-06-25	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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	RCV000768646	SCV000219222	benign	Breast and/or ovarian cancer	2017-01-18	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000284446	SCV000333833	likely benign	not specified	2015-08-12	criteria provided, single submitter	clinical testing
Cancer Genetics and Genomics Laboratory, British Columbia Cancer Agency	RCV000284446	SCV000586888	benign	not specified	2017-04-18	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000162536	SCV000683059	likely benign	Hereditary cancer-predisposing syndrome	2015-04-27	criteria provided, single submitter	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000111927	SCV000744647	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2017-06-28	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000284446	SCV000806925	benign	not specified	2017-01-30	criteria provided, single submitter	clinical testing
Mendelics	RCV000111927	SCV001140570	likely benign	Breast-ovarian cancer, familial, susceptibility to, 1	2019-05-28	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000111927	SCV001280878	likely benign	Breast-ovarian cancer, familial, susceptibility to, 1	2019-08-14	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001689608	SCV001474355	benign	not provided	2022-07-08	criteria provided, single submitter	clinical testing
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State	RCV000047951	SCV002025971	benign	Hereditary breast ovarian cancer syndrome	2021-11-16	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000284446	SCV002070411	benign	not specified	2018-06-22	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001689608	SCV002585648	likely benign	not provided	2024-07-01	criteria provided, single submitter	clinical testing	BRCA1: BP4, BP7
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000111927	SCV004016752	likely benign	Breast-ovarian cancer, familial, susceptibility to, 1	2023-07-07	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000284446	SCV004026785	benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
Breast Cancer Information Core (BIC) (BRCA1)	RCV000111927	SCV000144529	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 1	2010-12-17	no assertion criteria provided	clinical testing
Sharing Clinical Reports Project (SCRP)	RCV000111927	SCV000189335	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2011-03-02	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000111927	SCV000591408	benign	Breast-ovarian cancer, familial, susceptibility to, 1		no assertion criteria provided	clinical testing	The p.Gly911Gly variant has been identified in 12 out of 8424 proband chromosomes (frequency 0.001) in individuals with sporadic and familial breast and ovarian cancer phenotype; and was absent in 48 control chromosomes included in these studies (Judkins 2005, van der Hout 2006, Uhrhammer 2008, Caux-Moncoutier 2009, Borg 2010). It is listed in dbSNP database” (ID#: rs1800740) while no information was provided, however, in the exome server it is found in 5/8595 (frequency 0.0006) in European and 1/4405 (frequency 0.0003) in African populations, suggesting that this is a benign variant. In addition, in the UMD database, this variant has been identified in 2 (out of 43) individuals with breast or ovarian cancers, where a second pathogenic BRCA1 or BRCA2 mutation was also detected, further suggesting that this is a benign variant. In addition, it was identified by our laboratory in one individual with a second pathogenic variant. 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. In addition, in-silico or computational prediction software (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predicts no change in the splice site prediction score. In summary, based on above information this variant is classified as Benign
True Health Diagnostics	RCV000162536	SCV000886668	likely benign	Hereditary cancer-predisposing syndrome	2018-09-28	no assertion criteria provided	clinical testing
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV001689608	SCV001906299	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001689608	SCV001960138	likely benign	not provided		no assertion criteria provided	clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000047951	SCV002050293	benign	Hereditary breast ovarian cancer syndrome	2021-12-17	no assertion criteria provided	clinical testing