ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.2125_2126insAGT (p.Phe709Ter)

dbSNP: rs1555590428
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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) RCV000257077 SCV000323398 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2016-10-18 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 RCV000257077 SCV000325245 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2015-10-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000985381 SCV001133514 pathogenic not provided 2019-07-16 criteria provided, single submitter clinical testing The variant creates a premature nonsense codon, and is therefore predicted to result in the loss of a functional protein. Found in at least one symptomatic patient in literature, and not found in general population data.
Ambry Genetics RCV002418098 SCV002729946 pathogenic Hereditary cancer-predisposing syndrome 2020-03-20 criteria provided, single submitter clinical testing The c.2125_2126insAGT pathogenic mutation (also known as p.S708_F709ins*), located in coding exon 9 of the BRCA1 gene, results from an in-frame AGT insertion at nucleotide positions 2125 to 2126. This results in the insertion of stop codon between codons 708 and 709. This alteration was identified in a large, worldwide study of BRCA1/2 mutation positive families (Rebbeck TR et al. Hum. Mutat., 2018 05;39:593-620). This alteration was also reported in an individual with breast cancer who had a relative with ovarian cancer (Crawford B et al. Breast Cancer Res. Treat., 2017 Jun;163:383-390). 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.
Invitae RCV002518776 SCV003340165 pathogenic Hereditary breast ovarian cancer syndrome 2023-05-15 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Phe709*) 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). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 266220). This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 28281021).

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