ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.5576C>G (p.Pro1859Arg) (rs80357322)

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Total submissions: 14
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000112706 SCV000244406 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 = 0.00000104
Invitae RCV001084637 SCV000077069 likely benign Hereditary breast and ovarian cancer syndrome 2020-12-04 criteria provided, single submitter clinical testing
GeneDx RCV000168527 SCV000209995 likely benign not specified 2017-11-29 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.
Ambry Genetics RCV000162995 SCV000213483 benign Hereditary cancer-predisposing syndrome 2015-10-24 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000168527 SCV000219270 likely benign not specified 2017-02-14 criteria provided, single submitter clinical testing
Counsyl RCV000112706 SCV000489179 benign Breast-ovarian cancer, familial 1 2016-09-01 criteria provided, single submitter clinical testing
Color Health, Inc RCV000162995 SCV000683336 likely benign Hereditary cancer-predisposing syndrome 2016-04-25 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000590490 SCV000699275 benign not provided 2017-05-26 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.5576C>G (p.Pro1859Arg) variant involves the alteration of a non-conserved nucleotide and 2/4 in silico tools (SNPsandGO not captured due to low reliability index) predict a benign outcome. Multiple functional studies support these benign predictions, to which the variant was found to act comparable to wild type function for homology directed repair and transcription activation. This variant was found in 3/120890 control chromosomes at a frequency of 0.0000248, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA1 variant (0.0010005). Multiple publications have cited the variant in affected individuals, although with limited information (ie, lack of co-occurrence and/or cosegregation data). BIC has cited the variant to co-occur with a pathogenic BRCA2 variant, c.5073_5074insA (classified as pathogenic by LCA). Furthermore, multipe publications have predicted the variant to be "neutral," along with multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. Therefore, taking all available lines of evidence into consideration, the variant of interest has been classified as Benign.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000590490 SCV001133642 benign not provided 2018-10-08 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000168527 SCV001156922 likely benign not specified 2019-03-19 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000112706 SCV000145582 uncertain significance Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000168527 SCV000587523 benign not specified 2014-01-31 no assertion criteria provided research
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000590490 SCV000591641 uncertain significance not provided no assertion criteria provided clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000590490 SCV000778730 likely benign not provided 2017-09-18 no assertion criteria provided clinical testing

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