Submissions for variant NM_007294.4(BRCA1):c.2109A>G (p.Thr703=)

gnomAD frequency: 0.00147  dbSNP: rs4986844

Total submissions: 20

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000111772	SCV000578000	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 0.0052 (African), derived from ExAC (2014-12-17).
Invitae	RCV000047711	SCV000075724	benign	Hereditary breast ovarian cancer syndrome	2024-01-30	criteria provided, single submitter	clinical testing
GeneDx	RCV000173831	SCV000167250	benign	not specified	2013-11-04	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	RCV000162519	SCV000212913	likely benign	Hereditary cancer-predisposing syndrome	2014-07-23	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.
Counsyl	RCV000111772	SCV000220557	likely benign	Breast-ovarian cancer, familial, susceptibility to, 1	2014-07-30	criteria provided, single submitter	literature only
Eurofins Ntd Llc (ga)	RCV000173831	SCV000224987	benign	not specified	2014-10-07	criteria provided, single submitter	clinical testing
Michigan Medical Genetics Laboratories, University of Michigan	RCV000111772	SCV000267697	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2016-04-21	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000476210	SCV000540965	benign	Familial cancer of breast	2017-02-23	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001796720	SCV000602729	benign	not provided	2021-09-08	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000162519	SCV000683012	benign	Hereditary cancer-predisposing syndrome	2015-10-09	criteria provided, single submitter	clinical testing
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State	RCV000047711	SCV002025990	benign	Hereditary breast ovarian cancer syndrome	2022-04-19	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000173831	SCV002066484	benign	not specified	2019-07-14	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000162519	SCV002538092	benign	Hereditary cancer-predisposing syndrome	2020-04-28	criteria provided, single submitter	curation
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000735514	SCV003838904	likely benign	Breast and/or ovarian cancer	2023-01-18	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000173831	SCV004026792	benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
Breast Cancer Information Core (BIC) (BRCA1)	RCV000111772	SCV000144304	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 1	2002-05-29	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000173831	SCV000591370	benign	not specified		no assertion criteria provided	clinical testing	The p.Thr703Thr variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located near a splice junction, and is also listed in the dbSNP database as coming from a "clinical source" (rs4986844) with a MAF score of 0.001. And it was identified in varying frequencies in various ethnic groups from the HapMap project. It was also reported in 20/111260 proband chromosomes of individuals from HBOC families, and classified as a polymorphism in the study by Myriad; although no control chromosomes were tested to establish the variant’s frequency in the general population (Judkins_2005). In addition, the variant was also identified in the UMD (x4), BIC (x2), Exome Server and BOCs databases. In summary, based on the above information, the variant is classified as predicted benign.
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research	RCV000735514	SCV000863652	benign	Breast and/or ovarian cancer	2012-08-27	no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000173831	SCV002036046	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001796720	SCV002038271	likely benign	not provided		no assertion criteria provided	clinical testing