ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.6037A>T (p.Lys2013Ter) (rs80358840)

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Total submissions: 17
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000506478 SCV000602814 pathogenic not specified 2016-11-04 criteria provided, single submitter clinical testing
Ambry Genetics RCV000131111 SCV000186041 pathogenic Hereditary cancer-predisposing syndrome 2018-01-03 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)
Breast Cancer Information Core (BIC) (BRCA2) RCV000031597 SCV000146755 pathogenic Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Color RCV000131111 SCV000688963 pathogenic Hereditary cancer-predisposing syndrome 2015-03-06 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031597 SCV000327336 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000031597 SCV000220422 likely pathogenic Breast-ovarian cancer, familial 2 2014-06-17 criteria provided, single submitter literature only
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031597 SCV000300972 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 RCV000217667 SCV000278866 pathogenic not provided 2018-05-30 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA2 c.6037A>T at the cDNA level and p.Lys2013Ter (K2013X) at the protein level. 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, also published as BRCA2 6265A>T using alternate nomenclature, has been reported in association with breast, ovarian, and prostate cancer (Hamann 2002, Walsh 2011, Litton 2012, Cunningham 2014, Solano 2016, Annala 2017). We consider this variant to be pathogenic.
GeneKor MSA RCV000044827 SCV000693575 pathogenic Hereditary breast and ovarian cancer syndrome 2017-11-01 criteria provided, single submitter clinical testing
Human Genome Sequencing Center Clinical Lab,Baylor College of Medicine RCV000031597 SCV000839935 pathogenic Breast-ovarian cancer, familial 2 2018-02-23 criteria provided, single submitter clinical testing This c.6037A>T (p.Lys2013*), variant in exon 11 of the BRCA2 gene creates a stop codon which is predicted to lead to nonsense-mediated mRNA decay, which is a known disease mechanism for this gene. This variant has been reported in multiple hereditary breast and ovarian cancer patients (PMID: 17513806, 21913181, 22006311, 23961350, 24504028, 25111659). Therefore, the c.6037A>T (p.Lys2013*) variant in the BRCA2 gene is classified as pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000044827 SCV000918981 pathogenic Hereditary breast and ovarian cancer syndrome 2018-01-05 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.6037A>T (p.Lys2013X) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA2 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. One in silico tool predicts a damaging outcome for this variant. This variant is absent in 248784 control chromosomes. The variant has been reported in the literature in several HBOC affected individuals (e.g. Meindl_2002, Machado_2007, Song_2014, Litton_2011, Tarabeux_2014, Solano_2016). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000044827 SCV000072840 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-19 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys2013*) 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 affected with breast cancer, ovarian cancer, fallopian tube cancer, and prostate cancer (PMID: 11802209, 11897832, 17513806, 22006311, 24504028, 25111659, 24728189). This variant is also known as 6265A>T in the literature. ClinVar contains an entry for this variant (Variation ID: 38016). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000044827 SCV000605782 pathogenic Hereditary breast and ovarian cancer syndrome 2015-07-30 criteria provided, single submitter clinical testing The p.Lys2013X variant has been reported in >20 individuals with BRCA2-associate d cancers (Meindl 2002, Hamann 2002, Wappenschmidt 2005, Machado 2007, Walsh 201 1, Litton 2012, Solano 2012, Cunningham 2014, Maier 2014, Breast Cancer Informat ion Core (BIC) database). It was absent from large control studies. This nonsens e variant leads to a premature termination codon at position 2013, which is pred icted to lead to a truncated or absent protein. Heterozygous loss of BRCA2 funct ion is an established disease mechanism in hereditary breast and ovarian cancer (HBOC). In summary, this variant meets criteria to be classified as pathogenic f or HBOC in an autosomal dominant manner based upon the predicted impact to the p rotein and presence in affected individuals.
Mendelics RCV000044827 SCV000838831 pathogenic Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000217667 SCV000296643 pathogenic not provided 2015-07-23 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000044827 SCV000587818 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000031597 SCV000054204 pathogenic Breast-ovarian cancer, familial 2 2012-05-01 no assertion criteria provided clinical testing

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