ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.475+3A>G (rs81002795)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color RCV000772645 SCV000905897 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-16 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000258385 SCV000327081 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
GeneDx RCV000479466 SCV000568447 uncertain significance not provided 2016-10-11 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.475+3A>G or IVS5+3A>G and consists of an A>G nucleotide substitution at the +3 position of intron 5 of the BRCA2 gene. Using alternate nomenclature this variant would be defined as BRCA2 703+3A>G. Multiple in silico models predict this variant to weaken the nearby natural donor site, and to possibly cause abnormal gene splicing; however, in the absence of RNA or functional studies, the actual effect of this variant is unknown. This variant has been reported in two families with early-onset breast and/or ovarian cancer diagnoses, but affected status or other clinical information were not provided (Wagner 1999, Tea 2014). BRCA2 c.475+3A>G was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. The adenine (A) nucleotide that is altered is conserved through mammals. Based on currently available information, it is unclear whether BRCA2 c.475+3A>G is pathogenic or benign. We consider it to be a variant of uncertain significance.
Laboratoire de Biologie et Génétique du Cancer,Centre François Baclesse RCV000258385 SCV000538192 pathogenic Breast-ovarian cancer, familial 2 no assertion criteria provided clinical testing

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