ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.117_118del (p.Cys39_Asp40delinsTer)

dbSNP: rs80357972
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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) RCV000077484 SCV000299406 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Ambry Genetics RCV000162845 SCV000213332 pathogenic Hereditary cancer-predisposing syndrome 2021-12-14 criteria provided, single submitter clinical testing The c.117_118delTG pathogenic mutation, located in coding exon 2 of the BRCA1 gene, results from a deletion of two nucleotides at nucleotide positions 117 to 118, causing a translational frameshift with a predicted alternate stop codon (p.C39*). This alteration has been reported as a pathogenic mutation in multiple individuals from large cohorts of BRCA1/2 mutation carriers (Azzollini J et al. Eur. J. Intern. Med., 2016 Jul;32:65-71; Rebbeck TR et al. Hum. Mutat., 2018 May;39:593-620). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077484 SCV000324976 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2015-10-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759490 SCV000888835 pathogenic not provided 2022-09-15 criteria provided, single submitter clinical testing This frameshift variant alters the translational reading frame of the BRCA1 mRNA and causes the premature termination of BRCA1 protein synthesis. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). In the published literature, the variant has been reported in individuals with breast and/or ovarian cancer (PMIDs: 10755399 (2000), 2706268 (2016), 28888541 (2017), and 29446198 (2018)). Based on the available information, this variant is classified as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV001070624 SCV001235886 pathogenic Hereditary breast ovarian cancer syndrome 2023-03-28 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Cys39*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 54157). This variant is also known as 236delAG, 39delTG. This premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer (PMID: 10755399, 27062684). This variant is not present in population databases (gnomAD no frequency).
GeneDx RCV000759490 SCV001811623 pathogenic not provided 2020-11-06 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek 2016); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as c.236_237delTG and c.236delTG; Observed in individuals with BRCA1-related cancers (Osorio 2000, Diez 2003, Capalbo 2006, Azzollini 2016, Franzese 2019); This variant is associated with the following publications: (PMID: 16760289, 18528753, 12955716, 28392550, 27062684, 10755399, 31850198)
Color Diagnostics, LLC DBA Color Health RCV000162845 SCV002053223 pathogenic Hereditary cancer-predisposing syndrome 2021-03-08 criteria provided, single submitter clinical testing This variant deletes 2 nucleotides in exon 3 of the BRCA1 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in at least four suspected hereditary breast and ovarian cancer families (PMID: 10755399, 16760289, 27062684, 29446198). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV000735464 SCV003838911 pathogenic Breast and/or ovarian cancer 2021-06-24 criteria provided, single submitter clinical testing
Baylor Genetics RCV000077484 SCV004216830 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2023-02-16 criteria provided, single submitter clinical testing
Clinical Genetics Laboratory, Skane University Hospital Lund RCV000759490 SCV005197263 pathogenic not provided 2022-12-05 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077484 SCV000109282 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2010-06-28 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000077484 SCV000144356 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2002-05-29 no assertion criteria provided clinical testing
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735464 SCV000863601 pathogenic Breast and/or ovarian cancer 2009-07-08 no assertion criteria provided clinical testing

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