ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.700del (p.Ser234fs) (rs80359630)

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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000509624 SCV000608275 pathogenic Hereditary cancer-predisposing syndrome 2016-11-04 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Breast Cancer Information Core (BIC) (BRCA2) RCV000031661 SCV000147525 pathogenic Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing
Color RCV000509624 SCV000689026 pathogenic Hereditary cancer-predisposing syndrome 2015-04-06 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031661 SCV000327578 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000045101 SCV000591708 pathogenic Hereditary breast and ovarian cancer syndrome 2014-08-05 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031661 SCV000300347 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735597 SCV000863735 pathogenic Breast and/or ovarian cancer 2016-01-15 no assertion criteria provided clinical testing
GeneDx RCV000486024 SCV000568443 pathogenic not provided 2017-12-28 criteria provided, single submitter clinical testing This deletion of one nucleotide in BRCA2 is denoted c.700delT at the cDNA level and p.Ser234ProfsX7 (S234PfsX7) at the protein level. The normal sequence, with the base that is deleted in braces, is ATTTT[T]CCAA. The deletion causes a frameshift which changes a Serine to a Proline at codon 234, and creates a premature stop codon at position 7 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA2 c.700delT, also known as c.928delT and c.924delT using alternate nomenclature, has been observed in several hereditary breast cancer families (Nedelcu 2002, Giannini 2006, Sinilnikova 2006, Seong 2009). We consider this variant to be pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000045101 SCV000695027 pathogenic Hereditary breast and ovarian cancer syndrome 2017-04-07 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.700delT (p.Ser234Profs) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA2 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.846_847delCA/p.Ile283fs). One in silico tool predicts a damaging outcome for this variant. The variant of interest is absent in 109122 control chromosomes in the large, broad control population (ExAC). The variant has been reported in affected individuals in multiple studies (Kluska_BRCA1_BMC Medical Genetics_2015, Seong_BRCA1_Clin Gen_2009, Giannini_BRCA1&2_Breast Cancer Res Treat_2006). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. These evidences support the classification of this variant as pathogenic based upon ACMG guidelines. Taken together, this variant is classified as pathogenic.
Invitae RCV000045101 SCV000073114 pathogenic Hereditary breast and ovarian cancer syndrome 2018-05-11 criteria provided, single submitter clinical testing This sequence change deletes 1 nucleotide from exon 9 of the BRCA2 mRNA (c.700delT), causing a frameshift at codon 234. This creates a premature translational stop signal (p.Ser234Profs*7) and is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA2 are known to be pathogenic. This particular variant has been reported in the literature in individuals with a personal and/or family history of breast and/or ovarian cancer (PMID: 11938448, 22798144, 26843898, 19656164, 22762150). This variant is also known as 924delT or 928delT in the literature. For these reasons, this variant has been classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000031661 SCV000296691 pathogenic Breast-ovarian cancer, familial 2 2015-03-27 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000045101 SCV000587564 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000031661 SCV000054268 pathogenic Breast-ovarian cancer, familial 2 2011-08-16 no assertion criteria provided clinical testing

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