Submissions for variant NM_000059.4(BRCA2):c.-15A>C

gnomAD frequency: 0.00066  dbSNP: rs138705202

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000168528	SCV000210549	benign	not specified	2014-07-01	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.
Eurofins Ntd Llc (ga)	RCV000168528	SCV000227005	likely benign	not specified	2015-10-13	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000200285	SCV000252602	benign	Hereditary breast ovarian cancer syndrome	2024-02-01	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000579801	SCV000683384	likely benign	Hereditary cancer-predisposing syndrome	2015-11-16	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001811230	SCV000883522	likely benign	not provided	2020-02-09	criteria provided, single submitter	clinical testing
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State	RCV000200285	SCV002026003	likely benign	Hereditary breast ovarian cancer syndrome	2022-04-19	criteria provided, single submitter	clinical testing
Sharing Clinical Reports Project (SCRP)	RCV000031295	SCV000053900	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2009-09-24	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA2)	RCV000031295	SCV000145978	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2004-02-20	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001353547	SCV000591650	uncertain significance	Malignant tumor of breast		no assertion criteria provided	clinical testing	The c.-15A>C variant has been previously reported in the literature in one study that looked at in-silico analyses of variants in the 5' untranslated region of the gene (Ozreti 2010). However, this information was not useful in determining the clinical significance of this variant. It is possible that this variant may influence the binding of transcription factors and expression or processing of the BRCA2 mRNA transcript. However, there is limited data to support this claim. It is listed in the dbSNP database (ID#: rs138705202) with a “global minor allele frequency" of 0.001 (1000 genomes), but was not validated. It is possible that this variant is common in a population from a geographic origin that has not been tested by our laboratory such that the full spectrum of benign variation has not yet been defined for this gene and increasing the likelihood that this variant may be benign. However, we cannot rule out that this variant may be implicated in the phenotype of this individual. In summary, the clinical significance of this variant cannot be determined with certainty at this time. Therefore this variant is a variant of unknown significance (VUS).