ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.1909+1G>A (rs587781629)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129734 SCV000184540 likely pathogenic Hereditary cancer-predisposing syndrome 2017-09-14 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations at the canonical donor/acceptor sites (+/- 1, 2) without other strong (b-level) evidence supporting pathogenicity
Color RCV000129734 SCV000688732 likely pathogenic Hereditary cancer-predisposing syndrome 2018-07-17 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000238861 SCV000326635 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000238861 SCV000785268 pathogenic Breast-ovarian cancer, familial 2 2017-06-23 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000204822 SCV000591779 pathogenic Hereditary breast and ovarian cancer syndrome 2014-04-09 criteria provided, single submitter clinical testing
GeneDx RCV000160183 SCV000210526 likely pathogenic not provided 2018-10-23 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.1909+1G>A or IVS10+1G>A and consists of a G>A nucleotide substitution at the +1 position of intron 10 of the BRCA2 gene. Using alternate nomenclature, this variant would be defined as BRCA2 2137+1G>A. This variant destroys a canonical splice donor site and is predicted to cause abnormal gene splicing, leading to either an abnormal message that is subject to nonsense-mediated mRNA decay or to an abnormal protein product. This variant has been observed in individuals with a personal and/or family history of breast and/or ovarian cancer (Chong 2014, Frey 2015, Minucci 2015, Shirts 2016, Frey 2017, Marchetti 2018). This variant was also identified in a woman with both breast and ovarian cancer, who carried an additional BRCA1 pathogenic variant (Cardoso 2018). Based on the currently available information, we consider BRCA2 c.1909+1G>A to be a likely pathogenic variant.
Hereditary Cancer Genetics group,Vall d'Hebron Institute of Oncology RCV000204822 SCV000916364 pathogenic Hereditary breast and ovarian cancer syndrome 2019-03-01 no assertion criteria provided research
Integrated Genetics/Laboratory Corporation of America RCV000204822 SCV000694584 pathogenic Hereditary breast and ovarian cancer syndrome 2016-10-18 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.1909+1G>A variant involves the alteration of a conserved intronic nucleotide at the splicing site. One in silico tool predicts a damaging outcome for this variant. 4/5 splice prediction tools predict that this variant eliminates the 5' splicing donor site, which may lead to abnormal splicing and disrupted protein product. This variant has been reported in at least 6 HBOC patients and is absent in 115480 control chromosomes. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic/likely pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000204822 SCV000260614 likely pathogenic Hereditary breast and ovarian cancer syndrome 2018-11-07 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 10 of the BRCA2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals with ovarian and breast cancer (PMID: 26296696, 26845104, 24830819). ClinVar contains an entry for this variant (Variation ID: 141283). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000238861 SCV000296672 pathogenic Breast-ovarian cancer, familial 2 2015-05-11 criteria provided, single submitter clinical testing
University of Washington Department of Laboratory Medicine,University of Washington RCV000210109 SCV000266038 pathogenic Breast-ovarian cancer, familial 1 2015-11-20 criteria provided, single submitter clinical testing

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