ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.6938-1G>A

dbSNP: rs886040936
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000258239 SCV000327541 pathogenic Breast-ovarian cancer, familial, susceptibility to, 2 2015-10-02 criteria provided, single submitter clinical testing
Invitae RCV000801410 SCV000941184 pathogenic Hereditary breast ovarian cancer syndrome 2023-08-20 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This sequence change affects an acceptor splice site in intron 12 of the BRCA2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with clinical features of BRCA2-related conditions (PMID: 10923033, 21520333, 31214711). ClinVar contains an entry for this variant (Variation ID: 267667). Based on a multifactorial likelihood algorithm using genetic, in silico, and/or statistical data, this variant has been determined to have a high probability of being pathogenic (PMID: 31131967). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site.
Mendelics RCV000258239 SCV001139163 likely pathogenic Breast-ovarian cancer, familial, susceptibility to, 2 2019-05-28 criteria provided, single submitter clinical testing
Ambry Genetics RCV001025818 SCV001188080 likely pathogenic Hereditary cancer-predisposing syndrome 2019-03-31 criteria provided, single submitter clinical testing The c.6938-1G>A intronic variant results from a G to A substitution one nucleotide upstream from coding exon 12 of the BRCA2 gene. This variant has been detected in a Romanian breast cancer family (Negura L et al. Revista Romana de Medicina de Laborator. 2012 Dec;20(4):317-26). This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice acceptor site; however, direct evidence is unavailable. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic.
Cancer Genomics Lab, PINUM Cancer Hospital RCV000258239 SCV004011754 pathogenic Breast-ovarian cancer, familial, susceptibility to, 2 2023-03-30 no assertion criteria provided clinical testing

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