ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.7147dup (p.Tyr2383fs) (rs878853599)

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Total submissions: 5
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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 RCV000240985 SCV000327597 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) RCV000240985 SCV000301135 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 RCV000657275 SCV000779006 pathogenic not provided 2016-12-12 criteria provided, single submitter clinical testing This duplication of one nucleotide in BRCA2 is denoted c.7147dupT at the cDNA level and p.Tyr2383LeufsX9 (Y2383LfsX9) at the protein level. The normal sequence, with the base that is duplicated in brackets, is ATTT[dupT]ATCA. The duplication causes a frameshift which changes a Tyrosine to a Leucine at codon 2383, and creates a premature stop codon at position 9 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.
Integrated Genetics/Laboratory Corporation of America RCV000227767 SCV000695045 likely pathogenic Hereditary breast and ovarian cancer syndrome 2016-10-13 criteria provided, single submitter clinical testing Variant summary: This c.7147dupT variant in BRCA2 gene leads to that results in the loss of the 1023 amino acids of BRCA2 (~70%). This change is predicted to cause loss of normal protein function through protein truncation or nonsense-mediated mRNA decay. The variant is absent from the control dataset of ExAC and has not, to our knowledge, been reported in affected individuals via published reports. Lastly, the variant has been cited as Pathogenic by a reputable database/clinical laboratory. Taking together, the variant was classified as Likely Pathogenic.
Invitae RCV000227767 SCV000283309 pathogenic Hereditary breast and ovarian cancer syndrome 2018-11-12 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr2383Leufs*9) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 236897). 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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