ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.2077_2078insTA (p.Asp693fs)

dbSNP: rs80357595
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Total submissions: 7
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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) RCV000111760 SCV000299694 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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV000257894 SCV000219213 pathogenic Breast and/or ovarian cancer 2018-09-06 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000111760 SCV000325226 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2015-10-02 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001092623 SCV001249208 pathogenic not provided 2019-07-01 criteria provided, single submitter clinical testing
Invitae RCV001388123 SCV001588992 pathogenic Hereditary breast ovarian cancer syndrome 2020-04-20 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has been observed in individual(s) with ovarian cancer (PMID: 30606148). ClinVar contains an entry for this variant (Variation ID: 125535). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Asp693Valfs*9) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product.
Ambry Genetics RCV002415589 SCV002726739 pathogenic Hereditary cancer-predisposing syndrome 2019-05-23 criteria provided, single submitter clinical testing The c.2077_2078insTA pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from an insertion of two nucleotides at position 2077, causing a translational frameshift with a predicted alternate stop codon (p.D693Vfs*9). This alteration was reported in a Brazilian cohort of 158 ovarian cancer patients who underwent BRCA1/2 testing in a patient with a positive family history who had a stage IV high grade serous ovarian carcinoma diagnosed in her 40s (Cotrim DP et al. BMC Cancer, 2019 Jan;19:4). In addition to the information 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.
Breast Cancer Information Core (BIC) (BRCA1) RCV000111760 SCV000144290 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 no assertion criteria provided clinical testing

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