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
Ambry Genetics RCV000219635 SCV000277916 likely pathogenic Hereditary cancer-predisposing syndrome 2015-08-19 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
Color RCV000219635 SCV000683839 likely pathogenic Hereditary cancer-predisposing syndrome 2018-07-31 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
Invitae RCV000045114 SCV000073127 likely pathogenic Hereditary breast and ovarian cancer syndrome 2016-03-27 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. It also falls at the last nucleotide of exon 13 of the BRCA2 coding sequence. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with breast cancer and/or ovarian cancer (PMID: 22970155). ClinVar contains an entry for this variant (Variation ID: 52242). Nucleotide substitutions at the last nucleotide of the exon are relatively common causes of aberrant splicing (PMID: 17576681). Algorithms developed to predict the effect of nucleotide changes on mRNA splicing suggest that this variant may alter mRNA splicing. In addition, two other missense substitutions at this codon (p.Arg2336His and p.Arg2336Pro) are reported to cause a large exon skipping resulting in a truncated protein (PMID: 25447315, 21719596, 9150172). This indicates that this nucleotide may be crucial for normal mRNA splicing. For these reasons, this variant has been classified as Likely Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759653 SCV000889121 likely pathogenic not provided 2018-01-12 criteria provided, single submitter 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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