ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.5558A>G (p.Tyr1853Cys) (rs80357258)

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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 RCV000563885 SCV000665902 likely pathogenic Hereditary cancer-predisposing syndrome 2018-03-08 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Deficient protein function in appropriate functional assay(s),Structural Evidence,Rarity in general population databases (dbsnp, esp, 1000 genomes)
Breast Cancer Information Core (BIC) (BRCA1) RCV000112703 SCV000145576 uncertain significance Breast-ovarian cancer, familial 1 2002-06-20 no assertion criteria provided clinical testing
Color RCV000563885 SCV000908975 likely pathogenic Hereditary cancer-predisposing syndrome 2018-05-07 criteria provided, single submitter clinical testing
University of Washington Department of Laboratory Medicine,University of Washington RCV000757927 SCV000886445 likely pathogenic Hereditary breast and ovarian cancer syndrome 2018-05-03 criteria provided, single submitter research The BRCA1 variant designated as p.Y1853C (NM_007294.3:c.5558A>G, historically referred to as 5677A>G) was previously classified as a variant of uncertain significance and is now classified as likely pathogenic. Cosegregation analysis of one observed family was performed using analyze.myvariant.org (Rañola et al, 2018, PMID:28965303). Analysis of this family shows yields a likelihood ratio of 1.9 to 1 (Thompson, et al., 2003, PMID:290079) that this allele is causing cancer within the family. This BRCA1 amino acid position is highly conserved. The variant is not listed in population databases such as ExAC or gnomAD. Functional data suggests that this variant compromises the BRCT domain (Lee 2010, PMID:20516115). More recent functional data is consistent with earlier findings and also indicates that the variant leads to a non-functional protein (Findlay et al, 2018, PMID:30209399). The combined results are consistent with a classification of likely pathogenic. This variant is predicted to alter BRCA1 function and increase breast and ovarian cancer risk. This analysis was performed in conjunction with the family studies project as part of the University of Washington Find My Variant Study.

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