ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.632-3_632-2del (rs431825341)

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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 RCV000218264 SCV000277266 uncertain significance Hereditary cancer-predisposing syndrome 2015-07-16 criteria provided, single submitter clinical testing
Invitae RCV000233601 SCV000283289 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-11-21 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. However, an adjacent adenine (A) nucleotide at c.632-4 preserves the canonical AG splice acceptor site sequence. 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: 96837). 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.
GeneDx RCV000255648 SCV000321448 uncertain significance not provided 2016-04-12 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.632-3_632-2delCA or IVS7-3_IVS7-2delCA and consists of a deletion of two nucleotides at the -2 and -3 position of intron 7 of the BRCA2 gene. Using alternate nomenclature, this variant would be defined as BRCA2 860-3_860-2delCA. The normal sequence with the bases that are deleted in brackets is ctta[ca]gTCA, where the capital letters are exonic and lowercase are intronic. Multiple in silico models predict this variant to destroy the nearby natural 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.632-3_632-2delCA was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. The nucleotides that are deleted are conserved across species. Based on currently available information, it is unclear whether BRCA2 c.632-3_632-2delCA is pathogenic or benign. We consider it to be a variant of uncertain significance.
Color RCV000218264 SCV000906018 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-02 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000082958 SCV000115032 uncertain significance Breast-ovarian cancer, familial 2 2007-11-21 no assertion criteria provided clinical testing

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