Submissions for variant NM_000059.3(BRCA2):c.5704G>A (p.Asp1902Asn)

gnomAD frequency: 0.00655  dbSNP: rs4987048

Total submissions: 33

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000113464	SCV000245034	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2015-01-12	reviewed by expert panel	curation	Class 1 not pathogenic based on frequency >1% in an outbred sampleset. Frequency 0.01626 (African), derived from 1000 genomes (2012-04-30).
Invitae	RCV000167833	SCV000072736	benign	Hereditary breast ovarian cancer syndrome	2024-02-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000131020	SCV000185947	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: 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)	RCV000120340	SCV000202290	benign	not specified	2015-05-22	criteria provided, single submitter	clinical testing
Counsyl	RCV000113464	SCV000220271	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2014-04-28	criteria provided, single submitter	literature only
Vantari Genetics	RCV000131020	SCV000267018	likely benign	Hereditary cancer-predisposing syndrome	2015-12-21	criteria provided, single submitter	clinical testing
Michigan Medical Genetics Laboratories, University of Michigan	RCV000113464	SCV000267785	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2016-04-21	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000113464	SCV000383723	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	2018-10-29	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.
Illumina Laboratory Services, Illumina	RCV000314320	SCV000383724	likely benign	Fanconi anemia complementation group D1	2018-10-29	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). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000167833	SCV000494333	benign	Hereditary breast ovarian cancer syndrome	2014-02-11	criteria provided, single submitter	clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000424920	SCV000511549	likely benign	not provided	2016-06-23	criteria provided, single submitter	clinical testing	Converted during submission to Likely benign.
Baylor Genetics	RCV000462033	SCV000541052	benign	Familial cancer of breast	2017-02-23	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000113464	SCV000575756	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	2016-01-29	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000120340	SCV000593718	benign	not specified	2019-02-11	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000424920	SCV000602746	benign	not provided	2023-11-29	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000131020	SCV000683727	benign	Hereditary cancer-predisposing syndrome	2015-03-10	criteria provided, single submitter	clinical testing
GeneKor MSA	RCV000120340	SCV000693638	benign	not specified	2017-11-01	criteria provided, single submitter	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000113464	SCV000744475	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	2015-09-21	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000120340	SCV000805730	benign	not specified	2016-10-03	criteria provided, single submitter	clinical testing
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State	RCV000167833	SCV002025783	benign	Hereditary breast ovarian cancer syndrome	2021-11-16	criteria provided, single submitter	clinical testing
Genetics Program, Instituto Nacional de Cancer	RCV000167833	SCV002515124	benign	Hereditary breast ovarian cancer syndrome	2021-11-01	criteria provided, single submitter	research
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000113464	SCV004016863	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2023-07-07	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000120340	SCV004027445	benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000735573	SCV004240330	benign	Breast and/or ovarian cancer	2022-09-26	criteria provided, single submitter	clinical testing
ITMI	RCV000120340	SCV000084492	not provided	not specified	2013-09-19	no assertion provided	reference population
Breast Cancer Information Core (BIC) (BRCA2)	RCV000113464	SCV000146670	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2002-05-29	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000113464	SCV000591989	benign	Breast-ovarian cancer, familial, susceptibility to, 2		no assertion criteria provided	clinical testing	The BRCA2 p.Asp1902Asn was identified in 2 of 4284 chromosomes (frequency: 0.0005) from individuals with breast cancer, and was absent in control chromosomes from these studies (Borg 2010, Fackenthal 2005). It is listed in dbSNP (ID#: rs4987048) with a “global minor allele frequency" of 0.004 (1000 Genomes), and in the Exome Variant Server ESP project with a frequency of 0.018 in African American alleles. It is also reported in several populations from the HapMap project, including: HAPMAP-MEX (frequency: 0.031), HAPMAP-LWK (frequency: 0.034), and HapMap-HCB (frequency: 0.038), increasing the likelihood that this is a low frequency benign variant in certain populations of origin. This variant was identified in LOVD, in BIC 87X with no clinical importance, and in UMD 10X as a “neutral” variant where it was reported to co-occur with known pathogenic mutations in BRCA1 and BRCA2 (BRCA2 c.994dup (p.Ile332AsnfsX4), BRCA1 c.3607C>T (p.Arg1203X), BRCA1 c.755_761del (p.Arg252LeufsX44)), further increasing the likelihood that this variant is benign. The p.Asp1902 residue is not conserved in mammals and lower organisms, and computational analyses (PolyPhen2, SIFT, AlignGVGD) do not suggest a high likelihood of impact to the protein, although this information is not predictive enough to rule out pathogenicity. In summary, based on the above information, this variant is classified as benign.
Mayo Clinic Laboratories, Mayo Clinic	RCV000424920	SCV000778689	benign	not provided	2017-07-24	no assertion criteria provided	clinical testing
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research	RCV000735573	SCV000863711	uncertain significance	Breast and/or ovarian cancer	2002-12-04	no assertion criteria provided	clinical testing
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000120340	SCV001905994	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000120340	SCV001957885	benign	not specified		no assertion criteria provided	clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000167833	SCV001977034	benign	Hereditary breast ovarian cancer syndrome	2021-09-27	no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000120340	SCV001978397	benign	not specified		no assertion criteria provided	clinical testing