ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3253dup (p.Arg1085fs)

dbSNP: rs80357517
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Total submissions: 8
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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) RCV000077125 SCV000299899 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.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077125 SCV000325585 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2015-10-02 criteria provided, single submitter clinical testing
GeneDx RCV000483228 SCV000566135 pathogenic not provided 2020-06-23 criteria provided, single submitter clinical testing Frameshift 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; Observed in individuals with a personal or family history consistent with pathogenic variants in this gene (Casadei 2001, Azzolini 2016); 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.3372dupA; This variant is associated with the following publications: (PMID: 10660329, 27062684, 11556835)
Labcorp Genetics (formerly Invitae), Labcorp RCV000496900 SCV002172981 pathogenic Hereditary breast ovarian cancer syndrome 2021-10-25 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 54805). This premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer (PMID: 27062684). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg1085Lysfs*8) 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).
Ambry Genetics RCV004609302 SCV005100944 pathogenic Hereditary cancer-predisposing syndrome 2024-03-20 criteria provided, single submitter clinical testing The c.3253dupA pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a duplication of A at nucleotide position 3253, causing a translational frameshift with a predicted alternate stop codon (p.R1085Kfs*8). This alteration has been reported in multiple individuals with personal and/or family history consistent with breast and/or ovarian carcinoma (HBOC) syndrome (De Benedetti VM et al. Hum. Mutat.,1998;12:215; Azzollini J et al. Eur. J. Intern. Med., 2016 Jul;32:65-71; Rebbeck TR et al. Hum. Mutat., 2018 May;39:593-620). 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. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). As such, this alteration is interpreted as a disease-causing mutation.
Sharing Clinical Reports Project (SCRP) RCV000077125 SCV000108922 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2011-08-16 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000077125 SCV000144685 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2002-05-29 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto RCV000496900 SCV000587288 pathogenic Hereditary breast ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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