ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.2123C>A (p.Ser708Tyr) (rs80357182)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129531 SCV000184307 likely benign Hereditary cancer-predisposing syndrome 2017-12-19 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Other data supporting benign classification
GeneDx RCV000314335 SCV000329124 uncertain significance not provided 2018-06-26 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.2123C>A at the cDNA level, p.Ser708Tyr (S708Y) at the protein level, and results in the change of a Serine to a Tyrosine (TCT>TAT). Using alternate nomenclature, this variant would be defined as BRCA1 2242C>A. This variant has been observed in individuals with breast cancer, and displayed homology directed repair activity comparable to wild-type in an in vitro functional study (Lu 2015, Azzolini 2016). BRCA1 Ser708Tyr was observed at an allele frequency of 0.04% (12/30,780) in individuals of South Asian ancestry in large population cohorts (Lek 2016). This variant is located in the DNA binding domain and the RAD50 and STAT1 binding domains (Zhong 1999, Ouchi 2000, Narod 2004). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available information, it is unclear whether BRCA1 Ser708Tyr is pathogenic or benign. We consider it to be a variant of uncertain significance.
Mendelics RCV000709482 SCV000839274 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Color RCV000129531 SCV000910913 likely benign Hereditary cancer-predisposing syndrome 2016-11-15 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031028 SCV000053622 uncertain significance Breast-ovarian cancer, familial 1 2009-04-03 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000031028 SCV000144307 uncertain significance Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing

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