ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.1785_1803del (p.His595fs) (rs1555282073)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000657314 SCV000779045 pathogenic not provided 2017-04-13 criteria provided, single submitter clinical testing This deletion of 19 nucleotides in BRCA2 is denoted c.1785_1803del19 at the cDNA level and p.His595GlnfsX13 (H595QfsX13) at the protein level. Using alternate nomenclature, this variant would be defined as BRCA2 2013_2031del19. The surrounding sequence is TACA[del19]GGAA. The deletion causes a frameshift which changes a Histidine to a Glutamine at codon 595, and creates a premature stop codon at position 13 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. We consider this variant to be pathogenic.
Invitae RCV000817436 SCV000957996 pathogenic Hereditary breast and ovarian cancer syndrome 2018-10-29 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.His595Glnfs*13) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. 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: 545781). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.

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