ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.2150del (p.Cys717fs) (rs397507618)

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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 RCV000241041 SCV000326662 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000241041 SCV000300494 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000482272 SCV000568459 pathogenic not provided 2016-09-28 criteria provided, single submitter clinical testing This deletion of one nucleotide in BRCA2 is denoted c.2150delG at the cDNA level and p.Cys717LeufsX13 (C717LfsX13) at the protein level. The normal sequence, with the base that is deleted in braces, is CAGT[G]TGAA. The deletion causes a frameshift which changes a Cysteine to a Leucine at codon 717, 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.Compared with carriers of a single BRCA1 or BRCA2 variant, individuals who are double heterozygotes for a BRCA1 and BRCA2 variant do not seem to have a more severe phenotype (Neuhausen 2009, Leegte 2005, Friedman 1998). Functional studies have proposed that the effect of double heterozygosity is not cumulative and that BRCA1 may be dominant over the BRCA2 variant (Ludwig 1997, Leegte 2005).

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