ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.3G>T (p.Met1Ile) (rs80358650)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Breast Cancer Information Core (BIC) (BRCA2) RCV000031452 SCV000146000 pathogenic Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735545 SCV000863683 likely pathogenic Breast and/or ovarian cancer 2005-12-13 no assertion criteria provided clinical testing
Invitae RCV000496217 SCV000836298 pathogenic Hereditary breast and ovarian cancer syndrome 2018-03-20 criteria provided, single submitter clinical testing This sequence change affects the initiator methionine of the BRCA2 mRNA. The next in-frame methionine is located at codon 124, which could potentially rescue translational initiation. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with breast cancer (PMID: 26287763). ClinVar contains an entry for this variant (Variation ID: 37871). A different variant (c.3G>A) affecting the same codon observed here (initiator codon) has been reported in individuals affected with breast and/or ovarian cancer (PMID: 21203900, 21769658, 20104584), indicating that this residue may be critical for protein function. While this variant is expected to result in an absent protein product, possible rescue of translational initiation by the downstream methionine would lead to the disruption of the N-terminal part of the BRCA2 protein that interacts with PALB2 (residues 18-40), which is critical for BRCA2-mediated homologous recombinational DNA repair (PMID: 16793542, 22678057, 19369211). For these reasons, this variant has been classified as Pathogenic.
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000496217 SCV000587526 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000031452 SCV000054057 pathogenic Breast-ovarian cancer, familial 2 2008-09-25 no assertion criteria provided clinical testing

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