ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.6859_6863del (p.Arg2287fs) (rs398122568)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000478767 SCV000566500 pathogenic not provided 2015-05-04 criteria provided, single submitter clinical testing This deletion of 5 nucleotides in BRCA2 is denoted c.6859_6863delAGAAA at the cDNA level and p.Arg2287LeufsX4 (R2287LfsX4) at the protein level. The normal sequence, with the bases that are deleted in braces, is CAAA[AGAAA]CTTA. The deletion causes a frameshift, which changes an Arginine to a Leucine at codon 2287, and creates a premature stop codon at position 4 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Although This variant, also known as BRCA2 7087_7091delAGAAA using alternate nomenclature, has not, to our knowledge, been reported in the literature, the adjacent mutation BRCA2 c.6856delAAAAG, which also results in a frameshift at this residue (p.Arg2287LeufsX4), has been reported in at least one individual with early-onset prostate cancer (Edwards 2003, 2010). we consider this variant to be pathogenic.
Invitae RCV000800123 SCV000939823 pathogenic Hereditary breast and ovarian cancer syndrome 2019-01-07 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg2287Leufs*4) 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 been observed in at least one individual affected with prostate cancer (PMID: 12474142, 20043088). This variant is also known as 7084delAAAAG and 6856delAAAAG in the literature. ClinVar contains an entry for this variant (Variation ID: 91461). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Sharing Clinical Reports Project (SCRP) RCV000076978 SCV000108775 pathogenic Breast-ovarian cancer, familial 2 2008-08-13 no assertion criteria provided clinical testing

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