ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.7069_7070del (p.Leu2357fs) (rs80359636)

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Total submissions: 22
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000045136 SCV000885109 pathogenic not provided 2017-07-27 criteria provided, single submitter clinical testing
Ambry Genetics RCV000131032 SCV000185962 pathogenic Hereditary cancer-predisposing syndrome 2018-01-05 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) RCV000031664 SCV000147015 pathogenic Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Color RCV000131032 SCV000292173 pathogenic Hereditary cancer-predisposing syndrome 2015-04-07 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031664 SCV000327588 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000031664 SCV000488257 pathogenic Breast-ovarian cancer, familial 2 2016-02-04 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000031664 SCV000744510 pathogenic Breast-ovarian cancer, familial 2 2015-09-21 criteria provided, single submitter clinical testing
Department of Medical Genetics,Oslo University Hospital RCV000031664 SCV000605676 pathogenic Breast-ovarian cancer, familial 2 2015-07-01 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000195404 SCV000592097 pathogenic Hereditary breast and ovarian cancer syndrome 2014-06-23 criteria provided, single submitter clinical testing
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000031664 SCV000733293 pathogenic Breast-ovarian cancer, familial 2 no assertion criteria provided clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031664 SCV000282439 pathogenic Breast-ovarian cancer, familial 2 2016-04-22 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Geisinger Autism and Developmental Medicine Institute,Geisinger Health System RCV000031664 SCV000804428 pathogenic Breast-ovarian cancer, familial 2 2017-06-11 criteria provided, single submitter provider interpretation This 6 year old male with global developmental delays (at-risk for mild intellectual disability), ADHD, disruptive behavior, and mild overgrowth was found to carry a maternally inherited 2 bp deletion in the BRCA2 gene. The c.7069_7070delCT pathogenic variant in the BRCA2 gene, previously reported as 7297delCT using alternate nomenclature, has been published in association with early-onset breast cancer, ovarian cancer, and prostate cancer (Garvin et al., 1997; Zhang et al., 2011; Cunningham et al., 2014; Song et al., 2014; Ellingson et al., 2015; Decker et al., 2016). The deletion causes a frameshift and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Given that this is an adult-onset condition, the patient is not expected to be affected at this time. The patient's mother has not been formally evaluated in the oncology setting, so her current status is unknown.
GeneDx RCV000045136 SCV000210786 pathogenic not provided 2018-07-25 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA2 c.7069_7070delCT at the cDNA level and p.Leu2357ValfsX2 (L2357VfsX2) at the protein level. The normal sequence with the bases that are deleted in brackets is ATTT[delCT]GTCT. The deletion causes a frameshift, changing a Leucine to a Valine at codon 2357, and creates a premature stop codon at position 2 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.7069_7070delCT, previously reported as 7297delCT using alternate nomenclature, has been published in association with early-onset breast cancer, ovarian cancer, and prostate cancer (Garvin 1997, Zhang 2011, Cunningham 2014, Song 2014, Ellingson 2015, Decker 2016). We therefore consider this variant to be pathogenic.
Genologica Medica RCV000031664 SCV000577969 pathogenic Breast-ovarian cancer, familial 2 2017-01-01 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000195404 SCV000695036 pathogenic Hereditary breast and ovarian cancer syndrome 2017-08-07 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.7069_7070delCT (p.Leu2357Valfs) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g., c.7133C>G [p.Ser2378X], c.7180A>T [p.Arg2394X], and c.7360delA [p.Ile2454fs). One in silico tool predicts a damaging outcome for this variant. This variant was found in the large control database ExAC at a frequency of 0.000033 (4/121100 control chromosomes), which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). The variant has been identified in numerous patients in published reports (e.g., Thomassen_Acta Oncol_2008). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000195404 SCV000073149 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-26 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu2357Valfs*2) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs756538291, ExAC 0.006%). This variant has been reported in individuals affected with breast and ovarian cancer (PMID: 9429140, 21324516, 24504028, 24728189). This variant is also known as 7297delCT in the literature. ClinVar contains an entry for this variant (Variation ID: 38082). 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 RCV000195404 SCV000271332 pathogenic Hereditary breast and ovarian cancer syndrome 2015-12-15 criteria provided, single submitter clinical testing The p.Leu2357fs variant in BRCA2 has been identified in >30 individuals with BRC A2-associated cancers (Garvin 1997, Spearman 2008, Borg 2010, Caux-Moncoutier 20 11, Zhang 2011, Breast Cancer Information Core (BIC) database). This variant has also been identified in 4/66706 European chromosomes by the Exome Aggregation C onsortium (ExAC, http://exac.broadinstitute.org; dbSNP rs80359636). Please note that this frequency is low enough to be consistent with the frequency of heredit ary breast and ovarian cancer (HBOC) in the general population. This variant is predicted to cause a frameshift, which alters the protein?s amino acid sequence beginning at position 2357 and leads to a premature termination codon 2 amino ac ids downstream. This alteration is then predicted to lead to a truncated or abse nt protein. Heterozygous loss of function of the BRCA2 gene is an established di sease mechanism in individuals with HBOC. In addition, this variant was classifi ed as Pathogenic on April 22, 2016 by the ClinGen-approved ENIGMA expert panel ( ClinVar SCV000282439.1). In summary, this variant meets criteria to be classifie d as pathogenic for HBOC in an autosomal dominant manner based upon the predicte d impact to the protein.
Mendelics RCV000195404 SCV000838849 pathogenic Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Michigan Medical Genetics Laboratories,University of Michigan RCV000031664 SCV000196001 pathogenic Breast-ovarian cancer, familial 2 2014-11-03 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000045136 SCV000296725 pathogenic not provided 2015-02-17 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000195404 SCV000587883 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000031664 SCV000054271 pathogenic Breast-ovarian cancer, familial 2 2013-04-23 no assertion criteria provided clinical testing

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