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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