ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8594dupT (p.Leu2865Phefs) (rs80359721)

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Total submissions: 8
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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) RCV000077637 SCV000301294 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Invitae RCV000045570 SCV000073583 pathogenic Hereditary breast and ovarian cancer syndrome 2018-11-27 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu2865Phefs*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 reported in an individual affected with breast cancer (PMID: 20104584). It is also known as 8823insT in the literature. ClinVar contains an entry for this variant (Variation ID: 52631), and has other names for this variant as 8821insT or 8822insT. Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000165308 SCV000216030 pathogenic Hereditary cancer-predisposing syndrome 2017-11-14 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
GeneDx RCV000486599 SCV000568495 pathogenic not provided 2018-04-16 criteria provided, single submitter clinical testing This duplication of one nucleotide in BRCA2 is denoted c.8594dupT at the cDNA level and p.Leu2865PhefsX4 (L2865FfsX4) at the protein level. The normal sequence, with the base that is duplicated in brackets, is GCCT[dupT]ATTC. The duplication causes a frameshift which changes a Leucine to a Phenylalanine at codon 2865, 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. BRCA2 c.8594dupT, also reported as 8821insT and 8822insT using alternate nomenclature, has been reported in association with breast cancer (Borg 2010, Ding 2011). We consider this variant to be pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000486599 SCV000600817 pathogenic not provided 2016-12-05 criteria provided, single submitter clinical testing
Counsyl RCV000077637 SCV000677701 pathogenic Breast-ovarian cancer, familial 2 2016-12-02 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077637 SCV000109440 pathogenic Breast-ovarian cancer, familial 2 2012-05-10 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077637 SCV000147412 pathogenic Breast-ovarian cancer, familial 2 2003-10-29 no assertion criteria provided clinical testing

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