ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.2167A>G (p.Asn723Asp) (rs4986845)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 20
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) RCV000031035 SCV000244315 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 = 0.000000000317
Invitae RCV000167793 SCV000075752 benign Hereditary breast and ovarian cancer syndrome 2020-12-04 criteria provided, single submitter clinical testing
GeneDx RCV000173845 SCV000167251 benign not specified 2014-01-14 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.
CSER _CC_NCGL, University of Washington RCV000148398 SCV000190097 likely benign Malignant tumor of prostate 2014-06-01 criteria provided, single submitter research
Ambry Genetics RCV000162975 SCV000213463 benign Hereditary cancer-predisposing syndrome 2014-11-18 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.
Counsyl RCV000031035 SCV000220269 benign Breast-ovarian cancer, familial 1 2014-04-25 criteria provided, single submitter literature only
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000173845 SCV000225006 likely benign not specified 2016-01-11 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000167793 SCV000494350 benign Hereditary breast and ovarian cancer syndrome 2014-02-23 criteria provided, single submitter clinical testing
Institute for Biomarker Research,Medical Diagnostic Laboratories, L.L.C. RCV000167793 SCV000576444 likely benign Hereditary breast and ovarian cancer syndrome 2017-02-14 criteria provided, single submitter clinical testing
Color Health, Inc RCV000162975 SCV000683016 likely benign Hereditary cancer-predisposing syndrome 2014-12-16 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000173845 SCV000806911 benign not specified 2016-10-03 criteria provided, single submitter clinical testing
Mendelics RCV000031035 SCV001140581 benign Breast-ovarian cancer, familial 1 2019-05-28 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000031035 SCV001283973 uncertain significance Breast-ovarian cancer, familial 1 2019-01-09 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001289838 SCV001477835 benign none provided 2019-09-24 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031035 SCV000053629 likely benign Breast-ovarian cancer, familial 1 2008-08-11 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000031035 SCV000144316 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 RCV000173845 SCV000587192 benign not specified 2014-01-31 no assertion criteria provided research
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001353651 SCV000591371 likely benign Malignant tumor of breast no assertion criteria provided clinical testing The BRCA1 p.Asn723Asp variant was identified in an individual with hereditary prostate cancer (Zuhlke 2004), and in at least 20 other patients from a data set 55630 patients undergoing clinical BRCA1 mutation screening (Judkins 2005). The variant was also identified in HGMD, LOVD, the BIC database (26X with unknown clinical importance), and UMD (6X as a neutral variant). In UMD the variant was listed once as co-occurring with a known pathogenic mutation in BRCA1 (c.-200_80del (p.Met1SerfsX13)), and Judkins (2005) identified the variant in trans with a different pathogenic BRCA1 mutation (p.Cys64Tyr), increasing the likelihood that the p.Asn723Asp variant does not have clinical importance. This residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. Three in silico studies suggest that the variant is not pathogenic or of no clinical significance (Abkevich 2004, Easton 2007, Lindor 2012). The variant was listed in dbSNP (ID: rs4986845) “With non-pathogenic allele”, with a minor allele frequency of 0.002 (1000 Genomes Project). It was also identified in the NHLBI Exome Sequencing Project with a frequency of 0.007 in African American alleles, and in several HapMap populations including HAPMAP-MKK (frequency: 0.014), HAPMAP-LWK (frequency: 0.011) and HAPMAP-ASW (frequency: 0.01), increasing the likelihood that this is a low frequency benign polymorphism in certain populations of origin. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.
True Health Diagnostics RCV000162975 SCV000787896 likely benign Hereditary cancer-predisposing syndrome 2017-12-08 no assertion criteria provided clinical testing
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735455 SCV000863592 likely benign Breast and/or ovarian cancer 2013-09-16 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.