ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.4357+2T>G (rs80358152)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000483230 SCV000569301 pathogenic not provided 2016-08-16 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.4357+2T>G or IVS12+2T>G and consists of a T>G nucleotide substitution at the +2 position of intron 12 of the BRCA1 gene. Using alternate nomenclature, this variant would be defined as/ has previously been published as BRCA1 4476+2T>G. This variant destroys a canonical splice donor site and is predicted to cause abnormal gene splicing, leading to either an abnormal message that is subject to nonsense-mediated mRNA decay or to an abnormal protein product. This variant has been reported in at least two women with a history of serous ovarian cancer (Ratajska 2015, Koczkowska 2016) We consider this variant to be pathogenic. Based on the current evidence, we consider this variant to be pathogenic.
Color RCV000581212 SCV000688489 likely pathogenic Hereditary cancer-predisposing syndrome 2018-10-05 criteria provided, single submitter clinical testing
Invitae RCV000699035 SCV000827729 likely pathogenic Hereditary breast and ovarian cancer syndrome 2018-03-20 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 12 of the BRCA1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with ovarian cancer (PMID: 25366421, 27167707). ClinVar contains an entry for this variant (Variation ID: 91629). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Sharing Clinical Reports Project (SCRP) RCV000077146 SCV000108943 pathogenic Breast-ovarian cancer, familial 1 2012-09-24 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000077146 SCV000145071 pathogenic Breast-ovarian cancer, familial 1 1999-06-22 no assertion criteria provided clinical testing

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