ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3289dup (p.Ser1097fs) (rs80357686)

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Total submissions: 5
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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) RCV000257391 SCV000323585 pathogenic Breast-ovarian cancer, familial 1 2016-10-18 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Ambry Genetics RCV000221558 SCV000277407 pathogenic Hereditary cancer-predisposing syndrome 2014-11-28 criteria provided, single submitter clinical testing The c.3289dupA(also known as 3408insA)pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a duplication of A at nucleotide position 3289, causing a translational frameshift with a predicted alternate stop codon. Since frameshifts are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294).
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000257391 SCV000325601 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000586124 SCV000699015 likely pathogenic Hereditary breast and ovarian cancer syndrome 2016-10-05 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.3289dupA (p.Ser1097Lysfs) 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.3296del, p.Pro1099fs). One in silico tool predicts a damaging outcome for this variant. This variant was absent in 121276 control chromosomes. In addition, clinical diagnostic laboratories/reputable databases classified this variant as pathogenic/likely pathogenic. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as likely pathogenic until additional information is available.
Invitae RCV000586124 SCV001581912 pathogenic Hereditary breast and ovarian cancer syndrome 2020-10-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser1097Lysfs*6) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 233101). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.

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