Submissions for variant NM_000059.4(BRCA2):c.4686A>G (p.Gln1562=)

gnomAD frequency: 0.00026  dbSNP: rs28897730

Total submissions: 19

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000495537	SCV000579135	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	2017-06-29	reviewed by expert panel	curation	Synonymous substitution variant, with low bioinformatic likelihood to result in a splicing aberration (Splicing prior probability 0.02; http://priors.hci.utah.edu/PRIORS/).
GeneDx	RCV000123977	SCV000167370	benign	not specified	2014-01-14	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	RCV000162568	SCV000212984	likely benign	Hereditary cancer-predisposing syndrome	2014-10-21	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.
Invitae	RCV000195757	SCV000252608	benign	Hereditary breast ovarian cancer syndrome	2024-02-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000299697	SCV000383704	uncertain significance	Fanconi anemia complementation group D1	2018-01-13	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 did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina	RCV000495537	SCV000383705	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2018-01-13	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 did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000585192	SCV000602803	benign	not provided	2017-12-20	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000162568	SCV000683644	benign	Hereditary cancer-predisposing syndrome	2015-04-01	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000585192	SCV000692772	likely benign	not provided	2024-07-01	criteria provided, single submitter	clinical testing	BRCA2: BP4
PreventionGenetics, part of Exact Sciences	RCV000585192	SCV000805713	likely benign	not provided	2017-06-01	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000769697	SCV000901113	likely benign	Breast and/or ovarian cancer	2023-04-05	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000123977	SCV002071600	likely benign	not specified	2021-10-14	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000162568	SCV002533895	likely benign	Hereditary cancer-predisposing syndrome	2021-01-13	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000123977	SCV002550338	likely benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000495537	SCV004845717	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2024-02-05	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000123977	SCV000591921	benign	not specified		no assertion criteria provided	clinical testing	The BRCA2 p.Gln1562Gln variant was identified in at least 3 of 10576 proband chromosomes (frequency 0.0003) from individuals with breast cancer, ovarian cancer, or prostate cancer; however, control chromosomes from healthy individuals were not included in these studies (Caux-Moncoutier 2009, Caux-Moncoutier 2011, Edwards 2003). The p.Gln1562Gln variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. The variant was listed in dbSNP (ID: rs28897730) with a minor allele frequency of 0.0004 (1000 Genomes Project), and in the NHLBI Exome Sequencing Project with a frequency of 0.0007 in European American alleles, increasing the likelihood that this is a low frequency benign variant in certain populations of origin. The variant was reported in ClinVar by one laboratory (GeneDx as benign). In summary, based on the above information,this variant is classified as benign.
Mayo Clinic Laboratories, Mayo Clinic	RCV000585192	SCV000778677	likely benign	not provided	2017-02-10	no assertion criteria provided	clinical testing
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000585192	SCV001906025	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000585192	SCV001954266	likely benign	not provided		no assertion criteria provided	clinical testing