ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.1961del (p.Lys654fs) (rs80357522)

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Total submissions: 25
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
3DMed Clinical Laboratory Inc RCV000677808 SCV000803967 pathogenic Infiltrating duct carcinoma of breast 2017-09-14 criteria provided, single submitter clinical testing
A.C.Camargo Cancer Center / LGBM, A.C.Camargo Cancer Center RCV000414241 SCV000492455 pathogenic Neoplasm of the breast criteria provided, single submitter research
Ambry Genetics RCV000130764 SCV000185656 pathogenic Hereditary cancer-predisposing syndrome 2018-03-27 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)
Breast Cancer Information Core (BIC) (BRCA1) RCV000031019 SCV000144262 pathogenic Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000047660 SCV000324814 uncertain significance Hereditary breast and ovarian cancer syndrome 2016-02-16 criteria provided, single submitter clinical testing Interpretation was last updated within 1 year from 2/16/2016 10:54 AM
Color RCV000130764 SCV000688356 pathogenic Hereditary cancer-predisposing syndrome 2017-04-03 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031019 SCV000325202 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000031019 SCV000785270 pathogenic Breast-ovarian cancer, familial 1 2017-06-27 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000031019 SCV000744670 pathogenic Breast-ovarian cancer, familial 1 2015-09-21 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000047660 SCV000591357 pathogenic Hereditary breast and ovarian cancer syndrome criteria provided, single submitter clinical testing
Department of Pathology and Molecular Medicine,Queen's University RCV000047660 SCV000588035 pathogenic Hereditary breast and ovarian cancer syndrome 2017-04-20 criteria provided, single submitter clinical testing
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000031019 SCV000733652 pathogenic Breast-ovarian cancer, familial 1 no assertion criteria provided clinical testing
Division Human Genetics,Medical University Innsbruck RCV000031019 SCV000211994 pathogenic Breast-ovarian cancer, familial 1 2015-02-11 no assertion criteria provided clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031019 SCV000282269 pathogenic Breast-ovarian cancer, familial 1 2016-04-22 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000236783 SCV000292510 pathogenic not provided 2018-01-24 criteria provided, single submitter clinical testing This deletion of one nucleotide in BRCA1 is denoted c.1961delA at the cDNA level and p.Lys654SerfsX47 (K654SfsX47) at the protein level. The normal sequence, with the base that is deleted in brackets, is GAAAAAAA[delA]GTAC. The deletion causes a frameshift, which changes a Lysine to a Serine at codon 654, and creates a premature stop codon at position 47 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. BRCA1 c.1961delA, previously denoted as 2073delA and 2080delA using alternate nomenclature, has been reported in individuals with female and male breast cancer, ovarian cancer (Gayther 1995, Risch 2001, Diez 2003, Abugattas 2015, Couch 2015, de Juan 2015, Kang 2015) and as a recurrent variant in individuals of Spanish descent with breast and/or ovarian cancer (de Juan Jimenez 2013). We consider this variant to be pathogenic.
GeneKor MSA RCV000047660 SCV000693514 pathogenic Hereditary breast and ovarian cancer syndrome 2017-11-01 criteria provided, single submitter clinical testing
Genologica Medica RCV000031019 SCV000577925 pathogenic Breast-ovarian cancer, familial 1 2017-01-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000047660 SCV000403071 pathogenic Hereditary breast and ovarian cancer syndrome 2016-06-14 criteria provided, single submitter clinical testing The c.1961delA (p.Lys654SerfsTer47) variant (also commonly referred to as c.2080delA) results in a frameshift, and is predicted to result in premature termination of the protein. Across a selection of the available literature, the p.Lys654SerfsTer47 variant has been identified in a heterozygous state in 29 cases of breast or ovarian cancer (Gayther et al. 1995; Risch et al. 2001; Curci et al. 2002; Diez et al. 2003; Martinez-Ferrandis et al. 2003; Ahn et al. 2007; Kwon et al. 2008; Iyevleva et al. 2010; Kim et al. 2012; Kang et al. 2015; de Juan Jiminez et al. 2013; George et al. 2013; Abugattas et al. 2014; Silva et al. 2014). The variant was absent from 100 controls and is reported at a frequency of 0.00002 in the European (Non-Finnish) population of the Exome Aggregation Consortium Project but this is based on one allele so the variant is presumed to be rare. Most variants in the BRCA1 gene that have been shown to be associated with breast and ovarian cancer are frameshift variants resulting in a non-functional protein. Based on the potential impact of frameshift variants and the available evidence, the p.Lys654SerfsTer47 variant is classified as pathogenic for hereditary breast and ovarian cancer syndrome.
Integrated Genetics/Laboratory Corporation of America RCV000047660 SCV000698901 pathogenic Hereditary breast and ovarian cancer syndrome 2016-06-06 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.1961delA (p.Lys654Serfs) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA1 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.2001dupA, c.2299delA). One in silico tool predicts a damaging outcome for this variant. This variant was found in 1/121294 control chromosomes at a frequency of 0.0000082, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA1 variant (0.0010005). This variant has been reported in numerous HBOC patients. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000047660 SCV000075673 pathogenic Hereditary breast and ovarian cancer syndrome 2019-01-05 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys654Serfs*47) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs80357522, ExAC 0.001%). This variant has been reported in individuals affected with breast, ovarian, and endometrial cancer (PMID: 7493024, 12955716, 17645508, 23633455, 26026974). This variant is also known as 2073delA and 2080delA in the literature. ClinVar contains an entry for this variant (Variation ID: 37438). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Michigan Medical Genetics Laboratories,University of Michigan RCV000031019 SCV000195897 pathogenic Breast-ovarian cancer, familial 1 2014-11-03 criteria provided, single submitter clinical testing
PreventionGenetics RCV000236783 SCV000806905 pathogenic not provided 2017-03-16 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000236783 SCV000296329 pathogenic not provided 2015-04-24 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000047660 SCV000587176 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000031019 SCV000053612 pathogenic Breast-ovarian cancer, familial 1 2014-01-08 no assertion criteria provided clinical testing

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