Submissions for variant NM_007294.4(BRCA1):c.4636G>A (p.Asp1546Asn)

gnomAD frequency: 0.00006  dbSNP: rs28897691

Total submissions: 27

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000112369	SCV000244364	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2015-08-10	reviewed by expert panel	curation	IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 0.000173
Labcorp Genetics (formerly Invitae), Labcorp	RCV000048612	SCV000076625	benign	Hereditary breast ovarian cancer syndrome	2024-01-30	criteria provided, single submitter	clinical testing
GeneDx	RCV000123923	SCV000167307	benign	not specified	2013-12-13	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	RCV000162986	SCV000213474	benign	Hereditary cancer-predisposing syndrome	2014-09-03	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.
Counsyl	RCV000112369	SCV000220947	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2014-12-11	criteria provided, single submitter	literature only
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001811341	SCV000602726	benign	not provided	2020-02-05	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000162986	SCV000683196	likely benign	Hereditary cancer-predisposing syndrome	2015-07-22	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000112369	SCV000743391	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2014-10-09	criteria provided, single submitter	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000112369	SCV000744611	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2017-05-31	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000123923	SCV000806956	benign	not specified	2017-03-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000112369	SCV001280757	likely benign	Breast-ovarian cancer, familial, susceptibility to, 1	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Institute of Human Genetics, University of Leipzig Medical Center	RCV000112369	SCV001429384	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 1	2019-05-07	criteria provided, single submitter	clinical testing
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State	RCV000048612	SCV002025930	benign	Hereditary breast ovarian cancer syndrome	2021-11-16	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000123923	SCV002065803	likely benign	not specified	2021-08-24	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000162986	SCV002537762	likely benign	Hereditary cancer-predisposing syndrome	2021-03-19	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000123923	SCV002550971	benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000735456	SCV003838237	likely benign	Breast and/or ovarian cancer	2022-05-30	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000112369	SCV004016781	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2023-07-07	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001811341	SCV004140623	benign	not provided	2024-06-01	criteria provided, single submitter	clinical testing	BRCA1: BP4, BS1, BS2
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000048612	SCV004228047	benign	Hereditary breast ovarian cancer syndrome	2023-12-05	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV001811341	SCV005251035	benign	not provided		criteria provided, single submitter	not provided
Breast Cancer Information Core (BIC) (BRCA1)	RCV000112369	SCV000145135	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	RCV001353447	SCV000591529	benign	Malignant tumor of breast		no assertion criteria provided	clinical testing	The p.Asp1646Asn variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located near a splice junction, is listed in dbSNP (rs28897691) and EVS as a low frequency variant, and is reported as benign in XXX# publications (${MatchVariant_1_ReferenceSummary}).
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research	RCV000735456	SCV000863593	benign	Breast and/or ovarian cancer	2013-03-28	no assertion criteria provided	clinical testing
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000123923	SCV001906156	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000123923	SCV001959251	benign	not specified		no assertion criteria provided	clinical testing
BRCAlab, Lund University	RCV000112369	SCV004243978	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2020-03-02	no assertion criteria provided	clinical testing