ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.5456A>G (p.Asn1819Ser) (rs80357286)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001080025 SCV000077015 benign Hereditary breast and ovarian cancer syndrome 2020-11-23 criteria provided, single submitter clinical testing
Ambry Genetics RCV000131632 SCV000186655 benign Hereditary cancer-predisposing syndrome 2014-07-08 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.
GeneDx RCV000441215 SCV000527062 likely benign not specified 2017-02-02 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.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001282714 SCV000602704 likely benign none provided 2020-04-14 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000587361 SCV000699256 likely benign not provided 2016-03-24 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.5456A>G variant affects a non-conserved nucleotide, resulting in amino acid change from a medium size and polar Asparagine (N) to a small size and polar Serine (S). 4/4 in-silico tools predict benign outcome for this variant (SNPs&GO not captured due to low reliability index). Functional assays support these in silico predictions of a benign outcome. Homology directed recombination is not impaired by this missense mutation (Lu_BRCA_Nature Comms_2015), nor is the activity of this BRCT domain variant in transcriptional activation (Lee_CR_2010 ) . Pavlicek et al._2004 predicted the variant to lead to a conservative substitution also implicating a neutral outcome. This variant was found in 4/121402 control chromosomes at a frequency of 0.0000329, which does not significantly exceed maximal expected frequency of a pathogenic BRCA1 allele (0.0010005). There is at least one HBOC family reported to have the variant in the literature but this report lacks clinical, co-segregation, and control data, therefore it does not permit establishment of a cause-effect relationship between the variant and HBOC (Judkins_Cancer Res_2005). In addition, several reputable clinical laboratories classified this variant as benign without evidence to independently evaluate. There have been no reports of pathogenic co-occurrences in patients. Functional evidence strongly support a benign outcome, thus this missense BRCA1 variant is classified as likely benign until co-occurrence or co-segregation data are available.
Color Health, Inc RCV000131632 SCV000911447 benign Hereditary cancer-predisposing syndrome 2016-10-31 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000587361 SCV001133635 benign not provided 2019-05-30 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077625 SCV000109428 benign Breast-ovarian cancer, familial 1 2012-05-01 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000077625 SCV000145519 uncertain significance Breast-ovarian cancer, familial 1 1997-02-15 no assertion criteria provided clinical testing
Brotman Baty Institute,University of Washington RCV000077625 SCV001243910 not provided Breast-ovarian cancer, familial 1 no assertion provided in vitro

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