ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.4000_4001del (p.Leu1334fs) (rs398122775)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000077720 SCV000300693 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 RCV000160282 SCV000210742 pathogenic not provided 2014-06-05 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA2 c.4000_4001delTT at the cDNA level and p.Leu1334ArgfsX3 (L1334RfsX3) at the protein level. The normal sequence with the bases that are deleted in brackets is TAAC[TT]AGAA. The deletion causes a frameshift, changing a Leucine to an Arginine at codon 1334, and creating a premature stop codon at position 3 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 BRCA2 c.4000_4001delTT, also known as c.4228_4229delTT using alternate nomenclature, has not been previously reported to our knowledge, it is considered pathogenic.
Invitae RCV000637469 SCV000758929 pathogenic Hereditary breast and ovarian cancer syndrome 2017-12-28 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu1334Argfs*3) 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 reported in the literature in an individual affected with breast cancer (PMID: 26681312). ClinVar contains an entry for this variant (Variation ID: 91812). 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) RCV000077720 SCV000109523 pathogenic Breast-ovarian cancer, familial 2 2006-09-01 no assertion criteria provided clinical testing

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