ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5718_5719CT[2] (p.Leu1908fs) (rs80359530)

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Total submissions: 20
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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) RCV000009905 SCV000282413 pathogenic Breast-ovarian cancer, familial 2 2016-04-22 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Invitae RCV000044728 SCV000072741 pathogenic Hereditary breast and ovarian cancer syndrome 2019-01-05 criteria provided, single submitter clinical testing This sequence change deletes 2 nucleotides from exon 11 of the BRCA2 mRNA (c.5722_5723delCT), causing a frameshift at codon 1908. This creates a premature translational stop signal (p.Leu1908Argfs*2) and is expected to result in an absent or disrupted protein product. This variant has been reported to segregate with breast cancer in a single family (PMID: 23028338). It has also been reported in individuals affected with breast cancer (PMID: 8524414, 20927582, 22535016, 27553291), ovarian cancer (PMID: 21324516), prostate cancer (PMID: 20736950), and pancreatic cancer (PMID: 25940717, 24963353). This sequence change is also known as 5950delCT in the literature. ClinVar contains an entry for this variant (Variation ID: 9320). 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 RCV000131120 SCV000186050 pathogenic Hereditary cancer-predisposing syndrome 2018-01-19 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),Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation
Michigan Medical Genetics Laboratories,University of Michigan RCV000009905 SCV000195991 pathogenic Breast-ovarian cancer, familial 2 2014-11-03 criteria provided, single submitter clinical testing
GeneDx RCV000160297 SCV000210768 pathogenic not provided 2018-10-05 criteria provided, single submitter clinical testing This deletion of two nucleotides is denoted BRCA2 c.5722_5723delCT at the cDNA level and p.Leu1908ArgfsX2 (L1908RfsX2) at the protein level. The normal sequence, with the bases that are deleted in brackets, is CTCT[delCT]AGAT. The deletion causes a frameshift, which changes a Leucine to an Arginine at codon 1908, 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.5722_5723delCT, previously reported as 5950delCT, has been identified in individuals with early-onset and familial breast, male breast, ovarian, and pancreatic cancer (Wooster 1995, Frank 1998, Couch 2007, Cherbal 2010, de Juan 2015, Holter 2015, Johns 2017, Pritzlaff 2017). We consider this variant to be pathogenic.
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000735574 SCV000219360 pathogenic Breast and/or ovarian cancer 2017-07-25 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000160297 SCV000225178 pathogenic not provided 2015-05-04 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000044728 SCV000271330 pathogenic Hereditary breast and ovarian cancer syndrome 2015-11-13 criteria provided, single submitter clinical testing The p.Leu1908fs variant in BRCA2 has been reported in >40 individuals with BRCA2 -associated cancers (Kwong 2009, Cherbal 2010, Zhang 2011, Edwards 2010, Breast Cancer Information Core (BIC) database). While this variant was absent from larg e population studies, the ability of these studies to accurately detect indels m ay be limited. This variant is predicted to cause a frameshift, which alters the protein?s amino acid sequence beginning at position 1908 and leads to a prematu re termination codon 2 amino acids downstream. This alteration is then predicted 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 ovarian cancer (HBOC). In summary, this variant meets criteria to be classified as patho genic for HBOC in an autosomal dominant manner.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000160297 SCV000296745 pathogenic not provided 2015-01-30 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000009905 SCV000327270 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Baylor Genetics RCV000461157 SCV000541000 pathogenic Familial cancer of breast 2017-02-23 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000044728 SCV000591992 pathogenic Hereditary breast and ovarian cancer syndrome 2013-03-01 criteria provided, single submitter clinical testing
Department of Medical Genetics,Oslo University Hospital RCV000009905 SCV000605675 pathogenic Breast-ovarian cancer, familial 2 2015-07-01 criteria provided, single submitter clinical testing
Counsyl RCV000009905 SCV000677689 pathogenic Breast-ovarian cancer, familial 2 2015-05-27 criteria provided, single submitter clinical testing
Color RCV000131120 SCV000683728 pathogenic Hereditary cancer-predisposing syndrome 2015-05-05 criteria provided, single submitter clinical testing
OMIM RCV000009905 SCV000030126 pathogenic Breast-ovarian cancer, familial 2 1995-12-21 no assertion criteria provided literature only
Sharing Clinical Reports Project (SCRP) RCV000009905 SCV000054177 pathogenic Breast-ovarian cancer, familial 2 2013-03-28 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000009905 SCV000146677 pathogenic Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000044728 SCV000587796 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735574 SCV000863712 pathogenic Breast and/or ovarian cancer 2015-05-15 no assertion criteria provided clinical testing

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