ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.631+4A>G (rs397507841)

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Total submissions: 3
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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 RCV000258315 SCV000327387 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Department of Medical Genetics, Oslo University Hospital RCV000258315 SCV000605721 likely pathogenic Breast-ovarian cancer, familial 2 2017-07-17 criteria provided, single submitter clinical testing
Invitae RCV001379699 SCV001577546 likely pathogenic Hereditary breast and ovarian cancer syndrome 2020-05-13 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 been observed in individual(s) with a personal and/or family history of breast and ovarian cancer (PMID: 29339979, 29446198). ClinVar contains an entry for this variant (Variation ID: 52056). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 20455026, 31143303). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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