Submissions for variant NM_000059.4(BRCA2):c.198A>G (p.Gln66=)

gnomAD frequency: 0.00020  dbSNP: rs28897700

Total submissions: 22

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000113265	SCV000578005	benign	Breast-ovarian cancer, familial, susceptibility to, 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 0.0069 (South Asian), derived from ExAC (2014-12-17).
Invitae	RCV000167850	SCV000071946	benign	Hereditary breast ovarian cancer syndrome	2024-02-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000162901	SCV000213388	likely benign	Hereditary cancer-predisposing syndrome	2014-07-04	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.
Illumina Laboratory Services, Illumina	RCV000113265	SCV000383604	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	2018-01-13	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.
Illumina Laboratory Services, Illumina	RCV000377649	SCV000383605	likely benign	Fanconi anemia complementation group D1	2018-01-13	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.
Color Diagnostics, LLC DBA Color Health	RCV000162901	SCV000683467	likely benign	Hereditary cancer-predisposing syndrome	2015-04-02	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000499809	SCV000805662	benign	not specified	2017-09-01	criteria provided, single submitter	clinical testing
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State	RCV000167850	SCV002025782	benign	Hereditary breast ovarian cancer syndrome	2022-04-19	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000499809	SCV002070627	likely benign	not specified	2021-08-24	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000162901	SCV002533286	benign	Hereditary cancer-predisposing syndrome	2020-10-12	criteria provided, single submitter	curation
CeGaT Center for Human Genetics Tuebingen	RCV001723632	SCV002545106	benign	not provided	2022-10-01	criteria provided, single submitter	clinical testing	BRCA2: BP4, BP7, BS1, BS2
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000499809	SCV002550243	benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000167850	SCV002819231	benign	Hereditary breast ovarian cancer syndrome	2022-11-22	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000113265	SCV004016825	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2023-07-07	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003492348	SCV004240299	likely benign	Breast and/or ovarian cancer	2023-05-26	criteria provided, single submitter	clinical testing
Breast Cancer Information Core (BIC) (BRCA2)	RCV000113265	SCV000146362	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2010-09-18	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001353470	SCV000591663	benign	Malignant tumor of breast		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000499809	SCV001799685	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000499809	SCV001906460	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000499809	SCV001927093	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001723632	SCV001958213	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001723632	SCV001975933	likely benign	not provided		no assertion criteria provided	clinical testing