ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.8851G>A (p.Ala2951Thr) (rs11571769)

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Total submissions: 36
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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) RCV000114009 SCV000321230 benign Breast-ovarian cancer, familial 2 2016-09-28 reviewed by expert panel curation Class 1 not pathogenic based on frequency >1% in an outbred sampleset. Frequency 0.036 (Admixed American/Latino), 0.0215 (South Asian), derived from 1000 genomes (2013-05-02).
Invitae RCV000045643 SCV000073656 benign Hereditary breast and ovarian cancer syndrome 2020-12-04 criteria provided, single submitter clinical testing
Counsyl RCV000114009 SCV000154050 benign Breast-ovarian cancer, familial 2 2014-01-02 criteria provided, single submitter literature only
GeneDx RCV000120367 SCV000167416 benign not specified 2013-10-02 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.
Ambry Genetics RCV000128883 SCV000172740 benign Hereditary cancer-predisposing syndrome 2014-08-01 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.
Michigan Medical Genetics Laboratories,University of Michigan RCV000114009 SCV000196019 benign Breast-ovarian cancer, familial 2 2014-11-03 criteria provided, single submitter clinical testing
Pathway Genomics RCV000114009 SCV000223768 benign Breast-ovarian cancer, familial 2 2014-10-30 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000120367 SCV000227874 benign not specified 2015-07-30 criteria provided, single submitter clinical testing
Vantari Genetics RCV000128883 SCV000267027 benign Hereditary cancer-predisposing syndrome 2016-01-06 criteria provided, single submitter clinical testing
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia RCV000045643 SCV000296861 benign Hereditary breast and ovarian cancer syndrome 2015-10-20 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000768611 SCV000324842 benign Breast and/or ovarian cancer 2016-01-04 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000114009 SCV000383795 likely benign Breast-ovarian cancer, familial 2 2018-01-29 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. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Clinical Services Laboratory,Illumina RCV000322663 SCV000383796 likely benign Fanconi anemia, complementation group D1 2018-01-29 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). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000045643 SCV000494370 benign Hereditary breast and ovarian cancer syndrome 2014-02-04 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000034468 SCV000510683 benign not provided 2016-09-28 criteria provided, single submitter clinical testing
Color Health, Inc RCV000128883 SCV000537387 benign Hereditary cancer-predisposing syndrome 2014-12-30 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000120367 SCV000538465 benign not specified 2016-03-28 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: 3.5% (402/11526) Latino chromosomes
Baylor Genetics RCV000476344 SCV000541045 benign Familial cancer of breast 2017-02-23 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000114009 SCV000575751 likely benign Breast-ovarian cancer, familial 2 2015-12-07 criteria provided, single submitter clinical testing
Cancer Genetics and Genomics Laboratory,British Columbia Cancer Agency RCV000120367 SCV000586986 benign not specified 2017-04-18 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001282956 SCV000602773 benign none provided 2020-08-17 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000114009 SCV000743355 benign Breast-ovarian cancer, familial 2 2014-10-09 criteria provided, single submitter clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000114009 SCV000744552 benign Breast-ovarian cancer, familial 2 2015-09-21 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000120367 SCV000805788 benign not specified 2016-10-31 criteria provided, single submitter clinical testing
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034468 SCV000043234 no known pathogenicity not provided 2012-07-13 no assertion criteria provided research Converted during submission to Benign.
ITMI RCV000120367 SCV000084519 not provided not specified 2013-09-19 no assertion provided reference population
Breast Cancer Information Core (BIC) (BRCA2) RCV000114009 SCV000147474 benign Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Sharing Clinical Reports Project (SCRP) RCV000114009 SCV000189319 benign Breast-ovarian cancer, familial 2 2011-03-14 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001281077 SCV000592234 benign Malignant tumor of breast no assertion criteria provided clinical testing The p.Ala2951Thr variant has been reported in our laboratory as well as in the literature in 36/5864 (0.006 frequency) proband chromosomes and in 1/1018 control chromosomes (0.001 frequency) (Bergthorsson_2001_11389159, Borg_2010_20104584, Saxena_2006_17018160, Lin_2003_12815053, Spitzer_2000_10699917, Serova-Sinilnikova_1997_9150172, Weber_2006_16685647, Wagner_1999_9971877, Waddell_2008_18497862). It is listed in dbSNP database (ID#:rs11571769) but no frequency information was provided, and so the prevalence of this variant in the general population is not known. The p.Ala2951 residue is conserved across vertebrate species, and computational analyses (PolyPhen2, SIFT, AlignGVGD) suggest that the p.Ala2951Thr variant may impact the protein. However, this information is not predictive enough to assume pathogenicity. In one study, this variant did not co-segregate with cancer in three families, and its frequency in 4680 clinical samples was similar to that of the control population (Deffenbaugh_2002_12215251). Notably, this variant has been identified in the UMD database in a total of 15 individuals who had a second pathogenic variant (9 with BRCA2 mutations and 6 with BRCA1) and associated with a breast or ovarian cancer phenotype, increasing the likelihood that the p.Ala2951Thr variant does not have clinical significance. In addition, Myriad calls this variant as a polymorphism. In summary, based on the above information this variant is classified as benign.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000114009 SCV000733327 benign Breast-ovarian cancer, familial 2 no assertion criteria provided clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000034468 SCV000778721 likely benign not provided 2017-03-30 no assertion criteria provided clinical testing
True Health Diagnostics RCV000128883 SCV000787957 benign Hereditary cancer-predisposing syndrome 2017-09-13 no assertion criteria provided clinical testing
Center of Medical Genetics and Primary Health Care RCV001281077 SCV001451692 benign Malignant tumor of breast no assertion criteria provided clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000120367 SCV001799522 benign not specified no assertion criteria provided clinical testing
Clinical Genetics Laboratory, Department of Pathology,Netherlands Cancer Institute RCV000120367 SCV001906216 benign not specified no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000120367 SCV001952725 benign not specified no assertion criteria provided clinical testing

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