ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.2309C>G (p.Ser770Ter)

dbSNP: rs80357063
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Total submissions: 4
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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) RCV000256873 SCV000323435 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 RCV000256873 SCV000325320 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2015-10-02 criteria provided, single submitter clinical testing
Invitae RCV000812603 SCV000952921 pathogenic Hereditary breast ovarian cancer syndrome 2021-07-01 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser770*) 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 been observed in several families with high risk of breast and/or ovarian cancer (PMID: 29446198). ClinVar contains an entry for this variant (Variation ID: 266246). A different variant (c.2309C>A) giving rise to the same protein effect observed here (p.Ser770*) has been reported in individuals affected with breast and ovarian cancer (PMID: 9808526, 10866029, 22006311, 25452441). It is also known as c.2428C>A in the literature. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV002446502 SCV002735574 pathogenic Hereditary cancer-predisposing syndrome 2021-09-29 criteria provided, single submitter clinical testing The p.S770* pathogenic mutation (also known as c.2309C>G), located in coding exon 9 of the BRCA1 gene, results from a C to G substitution at nucleotide position 2309. This changes the amino acid from a serine to a stop codon within coding exon 9. 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 variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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.

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