ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9501+1G>T (rs397508058)

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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 RCV000258166 SCV000328147 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000779967 SCV000916932 likely pathogenic Hereditary breast and ovarian cancer syndrome 2017-10-05 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.9501+1G>T variant involves the alteration of a conserved intronic nucleotide. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict a significant impact on normal splicing -to abolish a canonical splice donor site. However, these predictions have yet to be confirmed by functional studies. This variant is absent in 276820 control chromosomes. The variant of interest has not, to our knowledge, been reported in affected individuals via publications. In addition, one other clinical diagnostic laboratory classified this variant as pathogenic. Taken together, this variant is classified as likely pathogenic, until more information becomes available.
Invitae RCV000779967 SCV000948172 likely pathogenic Hereditary breast and ovarian cancer syndrome 2018-11-01 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 25 of the BRCA2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals with increased risk of breast and/or ovarian cancer (PMID: 29446198). ClinVar contains an entry for this variant (Variation ID: 267725). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). 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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