ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.4168_4169del (p.Leu1390fs) (rs80359433)

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Total submissions: 4
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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 RCV000241006 SCV000326983 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) RCV000241006 SCV000300717 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 RCV000160285 SCV000210746 pathogenic not provided 2014-06-13 criteria provided, single submitter clinical testing This deletion of two nucleotides is denoted BRCA2 c.4168_4169delTT at the cDNA level and p.Leu1390GlyfsX12 (L1390Gfsx12) at the protein level. The normal sequence with the bases that are deleted in brackets is CTTTT[TT]GGAA. The deletion causes a frameshift, which changes a Leucine to a Glycine at codon 1390, and introduces a premature stop codon at position 12 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. BRCA2 c.4168_4169delTT is considered pathogenic.
Invitae RCV000822049 SCV000962831 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-30 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu1390Glyfs*12) 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 individuals with a personal or family history of breast and/or ovarian cancer (PMID: 26681312, 29446198). ClinVar contains an entry for this variant (Variation ID: 182314). 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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