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
Labcorp Genetics (formerly Invitae), Labcorp 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 2024-03-01 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). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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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