ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.632-3C>A (rs568027879)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000165268 SCV000215985 likely benign Hereditary cancer-predisposing syndrome 2020-08-07 criteria provided, single submitter clinical testing RNA Studies
Invitae RCV000464025 SCV000549764 uncertain significance Hereditary breast and ovarian cancer syndrome 2020-09-24 criteria provided, single submitter clinical testing This sequence change falls in intron 7 of the BRCA2 gene. It does not directly change the encoded amino acid sequence of the BRCA2 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA2-related disease. ClinVar contains an entry for this variant (Variation ID: 185781). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000507464 SCV000600694 uncertain significance not specified 2016-10-04 criteria provided, single submitter clinical testing
GeneDx RCV000766296 SCV000617999 uncertain significance not provided 2017-04-26 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.632-3C>A or IVS7-3C>A and consists of a C>A nucleotide substitution at the -3 position of intron 7 of the BRCA2 gene. Using alternate nomenclature, this variant would be defined as BRCA2 860-3C>A. Multiple in silico models predict this variant to damage or destroy the nearby natural splice acceptor site and to possibly cause 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.632-3C>A was not observed in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). The cytosine (C) nucleotide that is altered is not conserved. Based on currently available information, it is unclear whether BRCA2 c.632-3C>A is pathogenic or benign. We consider it to be a variant of uncertain significance.
Color Health, Inc RCV000165268 SCV000908706 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-28 criteria provided, single submitter clinical testing

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