ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.396C>A (p.Asn132Lys) (rs80357413)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 14
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000083203 SCV000244350 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 = 0.000166
Invitae RCV000587325 SCV000076408 benign not provided 2019-03-02 criteria provided, single submitter clinical testing
GeneDx RCV000212156 SCV000209906 likely benign not specified 2016-06-29 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 RCV000162966 SCV000213454 benign Hereditary cancer-predisposing syndrome 2014-11-18 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000212156 SCV000538447 uncertain significance not specified 2016-03-29 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: ExAC: 2/66738 European chromosomes; ClinVar: 3 labs B/LB, 1 lab VUS; at least 3 papers describe as non pathogenic
Institute for Biomarker Research,Medical Diagnostic Laboratories, L.L.C. RCV000083203 SCV000576447 likely benign Breast-ovarian cancer, familial 1 2017-02-14 criteria provided, single submitter clinical testing
Cancer Genetics and Genomics Laboratory,British Columbia Cancer Agency RCV000212156 SCV000586867 likely benign not specified 2017-04-18 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000212156 SCV000591262 likely benign not specified 2015-11-27 criteria provided, single submitter clinical testing
Color RCV000162966 SCV000683141 likely benign Hereditary cancer-predisposing syndrome 2016-06-06 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000587325 SCV000699090 benign not provided 2017-05-08 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.396C>A (p.Asn132Lys) variant (alternatively also known as 515C>A) involves the alteration of a non-conserved nucleotide and is not located in a known functional domain, while 4/5 in silico tools predict a damaging outcome for this variant. However, multiple functional studies demonstrated that this variant does not affect BRCA1 function (Towler_2013, Caligo_2009, Bouwman_2013, Maresca_2015, Thouvenot_2016). This variant was found in 2/121408 control chromosomes from ExAC at a frequency of 0.0000165, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA1 variant (0.0010005). This variant has been reported in several HBOC patients without clear evidence supporting causality. The variant of interest was found to co-occur with another pathogenic BRCA2 variant, c.4936_4939delGAAA (p.Glu1646fxX23 - classified as pathogenic by LCA) has been reported, supporting a benign outcome. Multifactorial probability based model integrating multiple forms of genetic evidence indicates that the variant is benign (Lindor_2012 and Easton_2007). In addition, multiple clinical diagnostic laboratories/reputable databases/publications classified this variant as benign/likely benign. Taken together, this variant is classified as benign.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000587325 SCV000887680 likely benign not provided 2017-10-07 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000083203 SCV000115277 likely benign Breast-ovarian cancer, familial 1 2009-11-13 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000083203 SCV000145271 uncertain significance Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000083203 SCV000733674 likely benign Breast-ovarian cancer, familial 1 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.