Submissions for variant NM_007294.4(BRCA1):c.981A>G (p.Thr327=)

gnomAD frequency: 0.00065  dbSNP: rs1800063

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)	RCV000111521	SCV000577997	benign	Breast-ovarian cancer, familial, susceptibility to, 1	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 0.0021 (Admixed American/Latino), derived from ExAC (2014-12-17).
Labcorp Genetics (formerly Invitae), Labcorp	RCV000049210	SCV000077223	benign	Hereditary breast ovarian cancer syndrome	2024-01-31	criteria provided, single submitter	clinical testing
Counsyl	RCV000111521	SCV000154013	likely benign	Breast-ovarian cancer, familial, susceptibility to, 1	2014-01-24	criteria provided, single submitter	literature only
Ambry Genetics	RCV000162537	SCV000212938	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	RCV000376504	SCV000219202	benign	not specified	2017-01-18	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000376504	SCV000333832	likely benign	not specified	2015-08-12	criteria provided, single submitter	clinical testing
Cancer Genetics and Genomics Laboratory, British Columbia Cancer Agency	RCV000376504	SCV000586876	benign	not specified	2017-04-18	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000162537	SCV000683380	likely benign	Hereditary cancer-predisposing syndrome	2015-04-27	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000376504	SCV000806988	benign	not specified	2017-01-30	criteria provided, single submitter	clinical testing
Mendelics	RCV000111521	SCV001140615	likely benign	Breast-ovarian cancer, familial, susceptibility to, 1	2019-05-28	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000111521	SCV001280984	likely benign	Breast-ovarian cancer, familial, susceptibility to, 1	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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001689611	SCV001474356	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	RCV000049210	SCV002026008	benign	Hereditary breast ovarian cancer syndrome	2021-11-16	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000376504	SCV002070500	benign	not specified	2018-06-22	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001689611	SCV002585650	likely benign	not provided	2024-08-01	criteria provided, single submitter	clinical testing	BRCA1: BP4, BP7
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000111521	SCV004016753	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	RCV000376504	SCV004026803	benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV001689611	SCV005251077	benign	not provided		criteria provided, single submitter	not provided
Breast Cancer Information Core (BIC) (BRCA1)	RCV000111521	SCV000143971	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 1	2011-07-08	no assertion criteria provided	clinical testing
Sharing Clinical Reports Project (SCRP)	RCV000111521	SCV000189351	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	RCV000376504	SCV000591310	benign	not specified		no assertion criteria provided	clinical testing	The p.Thr327Thr variant is not expected to have clinical significance because it does not alter an amino acid residue and is not located near a splice junction. It has been reported in the literature in 14/10588 proband chromosomes from individuals with hereditary and sporadic breast and/ or ovarian carcer (Alsop_2012_22711857, Borg_2010_20104584, Caux-Moncoutier_2011_21120943, Malone_1998_9544766, Stoppa-Lyonnet_1997_9150149, Tazzite_2012_22425665, Uhrhammer_2008_18645608); but it was not identified in the limited number (142) of control chromosomes evaluated. It is listed in dbSNP as coming from a "clinical source" (ID#: rs1800063), but no frequency information was provided, and so the prevalence of this variant in the general population is not known. The variant has been identified in the BIC database (x1), UMD database (x30) as likely neutral, and classified in the BOCs database (x1) as benign (ACMG 5). In addition, this variant has been identified by our laboratory in one individual with a second pathogenic mutation, increasing the likelihood this variant is benign. In summary, based on the above information, the p.Arg3370Arg variant is classified as benign.
True Health Diagnostics	RCV000162537	SCV000886670	likely benign	Hereditary cancer-predisposing syndrome	2018-09-28	no assertion criteria provided	clinical testing
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV001689611	SCV001905873	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001689611	SCV001960100	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000376504	SCV001965012	benign	not specified		no assertion criteria provided	clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000049210	SCV002050294	benign	Hereditary breast ovarian cancer syndrome	2021-12-17	no assertion criteria provided	clinical testing