ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8755-19A>G (rs398122713)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color RCV000776372 SCV000911800 likely benign Hereditary cancer-predisposing syndrome 2017-06-20 criteria provided, single submitter clinical testing
Counsyl RCV000077642 SCV000785049 likely benign Breast-ovarian cancer, familial 2 2018-06-13 criteria provided, single submitter clinical testing
GeneDx RCV000160155 SCV000210481 uncertain significance not provided 2018-05-01 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.8755-19A>G or IVS21-19A>G and consists of a A>G nucleotide substitution at the -19 position of intron 21 of the BRCA2 gene. Using alternate nomenclature, this variant would be defined as BRCA2 8983-19A>G. Multiple in silico models predict that this variant results in the gain of a cryptic splice acceptor site upstream of the natural splice acceptor site, possibly leading to abnormal gene splicing. However, in the absence of RNA or functional studies, the actual effect of this variant is unknown. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 c.8755-19A>G was not observed at a significant allele frequency in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). The adenine (A) nucleotide that is altered is not conserved. Based on currently available evidence, it is unclear whether BRCA2 c.8755-19A>G is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Integrated Genetics/Laboratory Corporation of America RCV000122936 SCV000494403 uncertain significance Hereditary breast and ovarian cancer syndrome 2016-09-09 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.8755-19A>G variant involves the alteration of a non-conserved intronic nucleotide. Mutation taster predicts a benign outcome for this variant while 5/5 in silico tools predict the variant to create a splice acceptor site in intron 21. This variant was found in 3/116166 control chromosomes at a frequency of 0.0000258, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). Multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available.
Invitae RCV000122936 SCV000166194 likely benign Hereditary breast and ovarian cancer syndrome 2017-10-31 criteria provided, single submitter clinical testing
PreventionGenetics RCV000160155 SCV000805784 uncertain significance not provided 2017-10-04 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077642 SCV000109445 likely benign Breast-ovarian cancer, familial 2 2014-06-11 no assertion criteria provided clinical testing

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