ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.7626G>A (p.Thr2542=) (rs61754138)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 18
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) RCV000113797 SCV000245116 benign Breast-ovarian cancer, familial 2 2015-01-12 reviewed by expert panel curation Class 1 not pathogenic based on frequency >1% in an outbred sampleset. Frequency 0.02033 (African), derived from 1000 genomes (2012-04-30).
Invitae RCV000045270 SCV000073283 benign Hereditary breast and ovarian cancer syndrome 2020-12-06 criteria provided, single submitter clinical testing
Counsyl RCV000113797 SCV000154047 likely benign Breast-ovarian cancer, familial 2 2014-01-02 criteria provided, single submitter literature only
GeneDx RCV000174985 SCV000167400 benign not specified 2013-10-24 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 RCV000162530 SCV000212928 benign Hereditary cancer-predisposing syndrome 2015-11-17 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.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000174985 SCV000226400 benign not specified 2014-09-30 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000045270 SCV000383771 likely benign Hereditary breast and ovarian cancer syndrome 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000276951 SCV000383772 likely benign Fanconi anemia 2016-06-14 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000045270 SCV000494353 benign Hereditary breast and ovarian cancer syndrome 2014-01-22 criteria provided, single submitter clinical testing
Baylor Genetics RCV000460388 SCV000541040 benign Familial cancer of breast 2017-02-23 criteria provided, single submitter clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C. RCV000045270 SCV000576436 likely benign Hereditary breast and ovarian cancer syndrome 2017-02-14 criteria provided, single submitter clinical testing
Color Health, Inc RCV000162530 SCV000683895 benign Hereditary cancer-predisposing syndrome 2015-04-02 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000174985 SCV000805767 benign not specified 2017-08-11 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000174985 SCV000883518 benign not specified 2018-10-25 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000113797 SCV000147150 uncertain significance Breast-ovarian cancer, familial 2 2010-12-17 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000174985 SCV000592133 benign not specified no assertion criteria provided clinical testing The BRCA2 p.Thr2542Thr variant was identified in 4 of 4500 proband chromosomes (frequency: 0.001) from individuals with breast and ovarian cancer (Borg 2010, Morgan 2010, Salazar 2006); however, control chromosomes were not evaluated in these studies, thus the prevalence of this variant in the general population could not be determined. Myriad classified the variant as a polymorphism (personal communication).The variant was also identified in dbSNP (ID: rs61754138) “With Likely Benign allele”, with a minor allele frequency of 0.0042(21 of 5000 chromosomes in 1000 Genomes Project). In NHLBI Exome Sequencing Project (Exome Variant Server), the variant was found in 27 of 4406 African American chromosomes and was not found in European American chromosomes, increasing the likelihood that this may be a low frequency benign variant in certain populations of origin. This variant was identified in the Exome Aggregation Consortium (ExAC) database, released Oct 20th, 2014) in 88 of 120570 chromosomes (frequency: 0.0007299) (or 76 of 10004 African individuals, 8 of 11522 of Latino, 4 of 66482of European (Finnish) chromosomes). The p.Thr2542Thr variant was identified in the ClinVar database (classified as a benign variant by ENIGMA, by Invitae, by GeneDx, Emory Genetics and as a likely benign by Counsyl and Ambry Genetics; as uncertain significance by BIC. In Clinvitae the variant was also identified by EmyClass as benign. BRCA share UMD database identified the variant as likely neutral 16X and co-occurred with BRCA2 pathogenic variants (c.8414_8416delinsC and c.IVS15-2A>T (c.7618-2A>T)) and BRCA1 pathogenic variants (c.211A>G (p.Arg71Gly) and c.IVS16+6T>C (c.4986+6T>C)), increasing the likelihood that the p.Thr2542Thr variant does not have clinical significance. The variant was identified in BIC database 2X with no clinical importance. The p.Thr2542Thr variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information, this variant meets our laboratory's criteria to be classified as benign.
Clinical Genetics Laboratory, Department of Pathology,Netherlands Cancer Institute RCV000174985 SCV001906167 benign not specified no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000174985 SCV001929604 benign not specified 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.