ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.7007G>T (p.Arg2336Leu) (rs28897743)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000045114 SCV000073127 likely pathogenic Hereditary breast and ovarian cancer syndrome 2018-08-09 criteria provided, single submitter clinical testing This sequence change replaces arginine with leucine at codon 2336 of the BRCA2 protein (p.Arg2336Leu). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and leucine. This variant also falls at the last nucleotide of exon 13 of the BRCA2 coding sequence, which is part of the consensus splice site for this exon. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with breast and/or ovarian cancer (PMID: 22970155, 27157322, 29446198). ClinVar contains an entry for this variant (Variation ID: 52242). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). 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. A different variant affecting this nucleotide (c.7007) has been determined to be pathogenic (PMID: 25447315, 21719596, 9150172). This suggests that this nucleotide is important for normal RNA splicing, and that other variants at this position may also be pathogenic. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Ambry Genetics RCV000219635 SCV000277916 likely pathogenic Hereditary cancer-predisposing syndrome 2015-08-19 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000113685 SCV000327567 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Color RCV000219635 SCV000683839 likely pathogenic Hereditary cancer-predisposing syndrome 2018-07-31 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759653 SCV000889121 likely pathogenic not provided 2018-01-12 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000113685 SCV000146993 pathogenic Breast-ovarian cancer, familial 2 2013-02-20 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000045114 SCV000587877 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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