ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.2773A>C (p.Ile925Leu) (rs4986847)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000162517 SCV000212911 benign Hereditary cancer-predisposing syndrome 2014-11-18 criteria provided, single submitter clinical testing
Baylor Genetics RCV000475644 SCV000540985 benign Familial cancer of breast 2017-02-23 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000031070 SCV000144543 uncertain significance Breast-ovarian cancer, familial 1 2004-02-20 no assertion criteria provided clinical testing
Color RCV000162517 SCV000688400 likely benign Hereditary cancer-predisposing syndrome 2016-05-16 criteria provided, single submitter clinical testing
Counsyl RCV000031070 SCV000488507 benign Breast-ovarian cancer, familial 1 2016-04-13 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000120274 SCV000591411 likely benign not specified 2015-05-19 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031070 SCV000244328 benign Breast-ovarian cancer, familial 1 2015-08-10 reviewed by expert panel curation IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 0.00000326
GeneDx RCV000120274 SCV000209946 likely benign not specified 2017-10-16 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
ITMI RCV000120274 SCV000084426 not provided not specified 2013-09-19 no assertion provided reference population
Integrated Genetics/Laboratory Corporation of America RCV000586756 SCV000698978 likely benign not provided 2017-04-20 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.2773A>C (p.Ile925Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. 3/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). This is also supported by multiple publications using multifactorial probability models (Lindor_HM_2012, Abkevich_J Med Genet_2004, Burk-Herrick_Mam Genome_2005). Also, this variant is not located in any known domain (InterPro). The variant of interest has been found in a large, broad control population, ExAC in 13/121378 control chromosomes predominantly observed in the African subpopulation at a frequency of 0.001154 (12/10402). This frequency is approximately equal to the estimated maximal expected allele frequency of a pathogenic BRCA1 variant (0.0010005), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. The variant of interest has been reported in multiple affected individuals via publications but no co-occurrence or co-segregation data was provided. Multiple clinical diagnostic laboratories/reputable databases recently (2016-2017) classified this variant as benign. Taken together, this variant is classified as likely benign until more functional and/or segregation studies become available.
Invitae RCV000195315 SCV000075980 benign Hereditary breast and ovarian cancer syndrome 2018-01-03 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031070 SCV000053666 likely benign Breast-ovarian cancer, familial 1 2006-06-20 no assertion criteria provided clinical testing

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