ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8754+4A>G (rs81002893)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000565525 SCV000665078 pathogenic Hereditary cancer-predisposing syndrome 2017-12-06 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Functionally-validated splicing mutation
Breast Cancer Information Core (BIC) (BRCA2) RCV000077450 SCV000147448 uncertain significance Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing
Color RCV000565525 SCV000904694 pathogenic Hereditary cancer-predisposing syndrome 2015-03-05 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077450 SCV000327956 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000077450 SCV000489073 likely pathogenic Breast-ovarian cancer, familial 2 2016-08-19 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000501422 SCV000592225 pathogenic Hereditary breast and ovarian cancer syndrome 2014-08-08 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000501422 SCV000695178 pathogenic Hereditary breast and ovarian cancer syndrome 2016-04-07 criteria provided, single submitter clinical testing Variant Summary: The variant of interest is located at a conserved intronic position, in which 5/5 splicing prediction programs via Alamut predict a loss (or weakening) effect on a canonical RNA splicing donor site. The variant of interest was not observed in controls (ExAC, 1000 Gs, ESP), but has been reported in multiple affected individuals via publications. Multiple independent functional studies show that this variant can cause a loss of intron 21 donor site, which leads to consequent activation of a cryptic splice site at position IVS21+46. The resulting transcript retained a 46-bp fragment of intron 21 and generates a stop codon at position c.IVS21+9, resulting in a truncated protein and consequently, suggesting a deleterious effect of this variant (Bontti_2006, Acedo_2014, and Houdayer_2012). In addition, multiple clinical laboratories/databases cite the variant with a classification of "Pathogenic/Causal." Therefore, taking all available lines of evidence into consideration, the variant of interest is classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000077450 SCV000296634 pathogenic Breast-ovarian cancer, familial 2 2015-11-18 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077450 SCV000109248 pathogenic Breast-ovarian cancer, familial 2 2012-05-01 no assertion criteria provided clinical testing

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