Submissions for variant NM_032043.3(BRIP1):c.2097+7G>A

gnomAD frequency: 0.00271  dbSNP: rs4988352

Total submissions: 26

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001079247	SCV000166676	benign	Familial cancer of breast; Fanconi anemia complementation group J	2024-02-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000124038	SCV000167447	benign	not specified	2013-10-22	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.
Illumina Laboratory Services, Illumina	RCV000412184	SCV000404601	likely benign	Fanconi anemia complementation group J	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.
Counsyl	RCV000412184	SCV000489809	likely benign	Fanconi anemia complementation group J	2016-06-03	criteria provided, single submitter	clinical testing
Counsyl	RCV000410211	SCV000489810	likely benign	Ovarian neoplasm	2016-06-03	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000123353	SCV000600897	benign	not provided	2022-06-30	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000579602	SCV000684182	likely benign	Hereditary cancer-predisposing syndrome	2015-03-18	criteria provided, single submitter	clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000579602	SCV000803168	likely benign	Hereditary cancer-predisposing syndrome	2018-05-23	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000124038	SCV000807126	benign	not specified	2017-05-22	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000124038	SCV000859954	likely benign	not specified	2018-03-12	criteria provided, single submitter	clinical testing
Mendelics	RCV000990005	SCV001140767	likely benign	Familial cancer of breast	2019-05-28	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000123353	SCV001151387	likely benign	not provided	2024-08-01	criteria provided, single submitter	clinical testing	BRIP1: BP4, BS2
Institute of Human Genetics, University of Leipzig Medical Center	RCV000990005	SCV001429190	uncertain significance	Familial cancer of breast	2018-09-19	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001798408	SCV002043626	likely benign	Breast and/or ovarian cancer	2023-04-25	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000124038	SCV002066274	benign	not specified	2021-04-16	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000579602	SCV002531392	benign	Hereditary cancer-predisposing syndrome	2020-10-19	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000124038	SCV002551178	likely benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000990005	SCV004019398	benign	Familial cancer of breast	2023-03-01	criteria provided, single submitter	clinical testing	This variant is considered benign. Homozygosity for this variant has been confirmed in one or more individuals lacking clinical features consistent with gene-specific recessive disease, indicating that this variant is unlikely to be pathogenic.
True Health Diagnostics	RCV000579602	SCV000805251	likely benign	Hereditary cancer-predisposing syndrome	2018-06-18	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001354110	SCV001548642	benign	Malignant tumor of breast		no assertion criteria provided	clinical testing	The BRIP1 c.2097+7G>A variant was identified in 3 of 436 proband chromosomes (frequency: 0.007) from individuals or families with breast or ovarian cancer and was identified in 1 of 146 control chromosomes (frequency: 0.005) from healthy individuals (Guenard_2008, Rutter_2003, Vahteristo_2006). The variant was also identified in dbSNP (ID: rs4988352) “With Uncertain significance allele”, ClinVar (classified benign by Invitae, GeneDx, likely benign by Counsyl, Quest Diagnostics Nichols Institute San Juan Capistrano and Color Genomics Inc, and uncertain significance by Illumina), Clinvitae (6x), Zhejiang Colon Cancer Database (7x), and was not identified in Cosmic or MutDB. The variant was identified in control databases in 644 of 277018 chromosomes (2 homozygous) at a frequency of 0.002 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). It was observed in the following populations: African in 8 of 24028 chromosomes (freq: 0.0003), Other in 10 of 6462 chromosomes (freq: 0.002), Latino in 72 of 34396 chromosomes (freq: 0.002), European Non-Finnish in 518 (1 homozygous) of 126558 chromosomes (freq: 0.004), European Finnish in 34 (1 homozygous) of 25788 chromosomes (freq: 0.001), and South Asian in 2 of 30780 chromosomes (freq: 0.00007); it was not observed in the Ashkenazi Jewish and East Asian populations. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign.
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000123353	SCV001806880	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000123353	SCV001906055	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000123353	SCV001926406	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000123353	SCV001952213	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000123353	SCV001972944	likely benign	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000123353	SCV002035522	likely benign	not provided		no assertion criteria provided	clinical testing