ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3286del (p.Gln1096fs)

gnomAD frequency: 0.00001  dbSNP: rs80357533
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Total submissions: 9
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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) RCV000112046 SCV000299909 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 RCV000217216 SCV000275826 pathogenic Hereditary cancer-predisposing syndrome 2023-05-23 criteria provided, single submitter clinical testing The c.3286delC pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of one nucleotide at nucleotide position 3286, causing a translational frameshift with a predicted alternate stop codon (p.Q1096Kfs*13). This alteration was identified in a breast/ovarian cancer family (Judkins, T et al. Cancer Res. 2005 Nov 1;65(21):10096-103). Of note, this alteration is also known as 3405delC in published literature. 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.
GeneDx RCV000484714 SCV000568414 pathogenic not provided 2023-07-03 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; Not observed at significant frequency in large population cohorts (gnomAD); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Observed in families with breast and/or ovarian cancer (Gayther et al., 1999; Naseem et al., 2006); Also known as 3405del; This variant is associated with the following publications: (PMID: 17026620, 26600092, 10486320, 30702160, 36169650, 16267036, 24631698, 28569743, 26269718)
Counsyl RCV000112046 SCV000677648 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2017-04-11 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001193113 SCV001361732 pathogenic Hereditary breast ovarian cancer syndrome 2019-12-16 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.3286delC (p.Gln1096LysfsX13) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the 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. The variant was absent in 250634 control chromosomes. c.3286delC has been reported in the literature in individuals affected with Breast and/or Ovarian Cancer (Judkins_2005, Naseem_2006, Bonds_2014). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV001193113 SCV002231953 pathogenic Hereditary breast ovarian cancer syndrome 2023-11-02 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln1096Lysfs*13) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 17026620). ClinVar contains an entry for this variant (Variation ID: 54819). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000112046 SCV004215084 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2023-06-23 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000217216 SCV004360238 pathogenic Hereditary cancer-predisposing syndrome 2023-10-19 criteria provided, single submitter clinical testing This variant deletes 1 nucleotide in exon 10 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. To our knowledge, functional studies have not been reported for this variant. This variant has been detected in an individual affected with breast cancer and a suspected hereditary breast and ovarian cancer family (PMID: 16267036; Color internal data). 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.
Breast Cancer Information Core (BIC) (BRCA1) RCV000112046 SCV000144699 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2003-12-23 no assertion criteria provided clinical testing

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