ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.516G>A (p.Lys172=) (rs80359790)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000044583 SCV000072596 uncertain significance Hereditary breast and ovarian cancer syndrome 2016-11-08 criteria provided, single submitter clinical testing This sequence change affects codon 172 of the BRCA2 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the BRCA2 protein. It also falls at the last nucleotide of exon 6 of the BRCA2 coding sequence. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the literature in an individual affected with breast and ovarian cancers (PMID: 19267246). ClinVar contains an entry for this variant (Variation ID: 51795). Nucleotide substitutions within the consensus splice site are relatively common causes of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of nucleotide changes on RNA splicing suggest that this variant may alter RNA splicing, and this prediction has been confirmed by a published transcriptional study in patient-derived RNA and in functional studies using exon trapping analysis in transfected cells (PMID: 19267246). In summary, this is a rare silent change that has been reported in an affected individual and has been shown to affect RNA splicing. However, in the absence of clinical evidence to prove the impact of this change on disease causation, it has been classified as a Variant of Uncertain Significance.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000113726 SCV000327154 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000113726 SCV000147045 uncertain significance Breast-ovarian cancer, familial 2 2001-10-29 no assertion criteria provided clinical testing

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