ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.4588A>T (p.Lys1530Ter) (rs80358692)

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Total submissions: 13
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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) RCV000077329 SCV000300769 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 RCV000044447 SCV000072460 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-06 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys1530*) 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 individuals with breast cancer (PMID: 26681312, 25452441). ClinVar contains an entry for this variant (Variation ID: 51678). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000212238 SCV000210339 pathogenic not provided 2018-02-27 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA2 c.4588A>T at the cDNA level and p.Lys1530Ter (K1530X) at the protein level. Using alternate nomenclature, this variant would be defined as BRCA2 4816A>T. The substitution creates a nonsense variant, which changes a Lysine to a premature stop codon (AAA>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been observed in at least one individual with breast cancer (Couch 2015). We consider BRCA2 Lys1530Ter to be pathogenic.
Ambry Genetics RCV000162921 SCV000213408 pathogenic Hereditary cancer-predisposing syndrome 2018-04-27 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)
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000077329 SCV000296632 pathogenic Breast-ovarian cancer, familial 2 2015-08-13 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077329 SCV000327057 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000077329 SCV000488190 likely pathogenic Breast-ovarian cancer, familial 2 2016-01-19 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000044447 SCV000605789 pathogenic Hereditary breast and ovarian cancer syndrome 2016-08-15 criteria provided, single submitter clinical testing The p.Lys1530X variant in BRCA2 has been reported in at least 9 individuals with BRCA2-associated cancers (Susswein 2015, Couch 2015, Breast Cancer Information Core (BIC) database), and was absent from large population studies. This nonsens e variant leads to a premature termination codon at position 1530, which is pred icted to lead to a truncated or absent protein. Heterozygous loss of function of the BRCA2 gene is an established disease mechanism in hereditary breast and ova rian cancer (HBOC). In summary, this variant meets our criteria to be classified as pathogenic for HBOC in an autosomal dominant manner based upon the predicted impact to the protein.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000212238 SCV000889053 pathogenic not provided 2015-08-13 criteria provided, single submitter clinical testing
Color RCV000162921 SCV000903414 pathogenic Hereditary cancer-predisposing syndrome 2017-11-09 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077329 SCV000109126 pathogenic Breast-ovarian cancer, familial 2 2012-01-30 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077329 SCV000146454 pathogenic Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000044447 SCV000587717 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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