Submissions for variant NM_000059.4(BRCA2):c.231T>G (p.Thr77=)

gnomAD frequency: 0.00191  dbSNP: rs114446594

Total submissions: 24

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000119247	SCV000321190	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2016-09-28	reviewed by expert panel	curation	Class 1 not pathogenic based on frequency >1% in an outbred sampleset. Frequency 0.0113 (African), derived from 1000 genomes (2013-05-02).
Labcorp Genetics (formerly Invitae), Labcorp	RCV000195302	SCV000071986	benign	Hereditary breast ovarian cancer syndrome	2024-02-01	criteria provided, single submitter	clinical testing
Counsyl	RCV000119247	SCV000154083	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	2014-03-14	criteria provided, single submitter	literature only
Ambry Genetics	RCV000129199	SCV000183943	benign	Hereditary cancer-predisposing syndrome	2014-11-19	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Eurofins Ntd Llc (ga)	RCV000176971	SCV000228765	benign	not specified	2014-12-29	criteria provided, single submitter	clinical testing
Michigan Medical Genetics Laboratories, University of Michigan	RCV000119247	SCV000267726	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2016-04-21	criteria provided, single submitter	clinical testing
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000195302	SCV000296852	likely benign	Hereditary breast ovarian cancer syndrome	2015-11-30	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000176971	SCV000538469	likely benign	not specified	2016-03-28	criteria provided, single submitter	clinical testing	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: ClinVar: 5 B/LB; Silent (meets our criteria for LB)
Baylor Genetics	RCV000466597	SCV000541058	benign	Familial cancer of breast	2017-02-23	criteria provided, single submitter	clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000195302	SCV000576432	likely benign	Hereditary breast ovarian cancer syndrome	2017-02-14	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000176971	SCV000602827	benign	not specified	2016-11-17	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000129199	SCV000683478	benign	Hereditary cancer-predisposing syndrome	2015-03-10	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000176971	SCV000805671	benign	not specified	2016-12-08	criteria provided, single submitter	clinical testing
Mendelics	RCV000119247	SCV001138949	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2019-05-28	criteria provided, single submitter	clinical testing
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State	RCV000195302	SCV002025793	benign	Hereditary breast ovarian cancer syndrome	2021-11-16	criteria provided, single submitter	clinical testing
University of Science and Technology Houari Boumediene, Laboratory of Molecular and Cellular Biology (LBCM)	RCV000119247	SCV002318936	benign	Breast-ovarian cancer, familial, susceptibility to, 2		criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000129199	SCV002533307	benign	Hereditary cancer-predisposing syndrome	2020-09-29	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000176971	SCV002761132	likely benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002496687	SCV002809037	benign	Familial cancer of breast; Breast-ovarian cancer, familial, susceptibility to, 2; Fanconi anemia complementation group D1; Medulloblastoma; Wilms tumor 1; Malignant tumor of prostate; Pancreatic cancer, susceptibility to, 2; Glioma susceptibility 3	2022-03-18	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003149670	SCV003838813	likely benign	Breast and/or ovarian cancer	2023-06-06	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001353938	SCV000591665	benign	Malignant tumor of breast		no assertion criteria provided	clinical testing	The p.Thr77Thr variant has been identified in 22 out of 1134 proband chromosomes (frequency 0.019) in individuals with breast and ovarian cancer phenotype, and was not identified in 300 control chromosomes (Cherbal 2010, Hadjisawas 2004, Hadjisawas 2003, Fackenthal 2011, Baumbach-abstract). However, it is listed in dbSNP database (ID#: rs114446594) with an average heterozygosity of 0.005+/-0.051, therefore increasing the likelihood of this variant to be benign. This 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. In the UMD database, this variant has been identified in 3 (out of 10) individuals with breast or ovarian cancers, where a second pathogenic BRCA1 or BRCA2 mutation was also detected, suggesting that this is a benign variant. In a recent study, partial exon 3 skipping was suggested to be associated with this variant, however this information is not very predictive of pathogenicity (Thery 2011). In summary, based on above information we would lean towards a more benign role for this variant, therefore this variant is classified as Benign.
Mayo Clinic Laboratories, Mayo Clinic	RCV000656582	SCV000778633	likely benign	not provided	2017-08-02	no assertion criteria provided	clinical testing
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000176971	SCV001906238	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000656582	SCV001972368	likely benign	not provided		no assertion criteria provided	clinical testing