ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.7008-5T>C (rs397507380)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000587746 SCV000321481 uncertain significance not provided 2018-07-30 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.7008-5T>C or IVS13-5T>C and consists of a T>C nucleotide substitution at the -5 position of intron 13 of the BRCA2 gene. Using alternate nomenclature, this variant would be defined as BRCA2 7236-5T>C. In silico analysis, which includes splice predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; however, in the absence of RNA or functional studies, the actual effect of this variant is unknown.? This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. BRCA2 c.7008-5T>C was not observed in large population cohorts. Based on currently available evidence, it is unclear whether BRCA2 c.7008-5T>C is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000456457 SCV000549851 uncertain significance Hereditary breast and ovarian cancer syndrome 2017-07-27 criteria provided, single submitter clinical testing This sequence change falls in intron 13 of the BRCA2 gene. It does not directly change the encoded amino acid sequence of the BRCA2 protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA2-related disease. ClinVar contains an entry for this variant (Variation ID: 38078). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000255121 SCV000600729 uncertain significance not specified 2016-09-13 criteria provided, single submitter clinical testing
Ambry Genetics RCV000575836 SCV000668821 uncertain significance Hereditary cancer-predisposing syndrome 2017-07-11 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Color RCV000575836 SCV000689025 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-13 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000587746 SCV000695026 uncertain significance not provided 2016-11-07 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.7008-5T>C variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant is absent in 120432 control chromosomes. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available.
Sharing Clinical Reports Project (SCRP) RCV000031660 SCV000054267 uncertain significance Breast-ovarian cancer, familial 2 2011-03-03 no assertion criteria provided clinical testing

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