ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.4676-2A>G (rs80358096)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131824 SCV000186879 likely pathogenic Hereditary cancer-predisposing syndrome 2016-09-08 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations at the canonical donor/acceptor sites (+/- 1, 2) without other strong (b-level) evidence supporting pathogenicity
Invitae RCV000477221 SCV000549272 likely pathogenic Hereditary breast and ovarian cancer syndrome 2016-09-27 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 14 of the BRCA1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with a BRCA1-related disease. ClinVar contains an entry for this variant (Variation ID: 125726). In summary, donor and acceptor splice site variants are typically truncating (PMID: 16199547), and truncating variants in BRCA1 are known to be pathogenic (PMID: 20104584). However, without additional functional and/or genetic data, this variant has been classified as Likely Pathogenic.
GeneDx RCV000480901 SCV000573033 pathogenic not provided 2017-02-03 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.4676-2A>G or IVS14-2A>G and consists of an A>G nucleotide substitution at the -2 position of intron 14 of the BRCA1 gene. This variant destroys a canonical splice acceptor 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, also defined as BRCA1 4795-2A>G using alternate nomenclature, has been reported in association with breast and/or ovarian cancer (Sekine 2001, Nakamura 2015). Based on the currently available information, we consider this variant to be pathogenic.
Breast Cancer Information Core (BIC) (BRCA1) RCV000112382 SCV000145154 pathogenic Breast-ovarian cancer, familial 1 2002-06-20 no assertion criteria provided clinical testing

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