ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.2138A>T (p.Gln713Leu) (rs55816687)

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Total submissions: 19
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001083754 SCV000071963 benign Hereditary breast and ovarian cancer syndrome 2020-12-07 criteria provided, single submitter clinical testing
GeneDx RCV000679159 SCV000108605 likely benign not provided 2021-05-17 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 26332594, 24055113, 15744044, 12474142, 24728327, 19491284, 23231788, 12491487, 25556971, 22034289, 25637381, 28814288, 18284688)
Ambry Genetics RCV000131496 SCV000186485 benign Hereditary cancer-predisposing syndrome 2018-09-11 criteria provided, single submitter clinical testing Co-occurence with a mutation in another gene that clearly explains a proband's phenotype;Co-occurence with mutation in same gene (phase unknown);In silico models in agreement (benign);Subpopulation frequency in support of benign classification
Michigan Medical Genetics Laboratories,University of Michigan RCV000077272 SCV000195967 likely benign Breast-ovarian cancer, familial 2 2014-11-03 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000679159 SCV000805666 likely benign not provided 2017-07-11 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000120312 SCV000859227 likely benign not specified 2018-01-16 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000679159 SCV000885100 likely benign not provided 2017-07-17 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000679159 SCV000889004 benign not provided 2018-07-31 criteria provided, single submitter clinical testing
Color Health, Inc RCV000131496 SCV000902740 benign Hereditary cancer-predisposing syndrome 2016-05-24 criteria provided, single submitter clinical testing
Mendelics RCV000077272 SCV001139022 benign Breast-ovarian cancer, familial 2 2019-05-28 criteria provided, single submitter clinical testing
ITMI RCV000120312 SCV000084464 not provided not specified 2013-09-19 no assertion provided reference population
Sharing Clinical Reports Project (SCRP) RCV000077272 SCV000109069 uncertain significance Breast-ovarian cancer, familial 2 2008-03-24 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077272 SCV000146011 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Pathway Genomics RCV000077272 SCV000187737 likely benign Breast-ovarian cancer, familial 2 2014-12-11 no assertion criteria provided clinical testing
CSER _CC_NCGL, University of Washington RCV000148430 SCV000190129 uncertain significance Breast neoplasm 2014-06-01 no assertion criteria provided research
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001353536 SCV000591791 likely benign Malignant tumor of breast no assertion criteria provided clinical testing The BRCA2 p.Gln713Leu variant was identified in 51 of 1748 proband chromosomes (frequency: 0.03) from individuals or families with prostate, breast and ovarian cancer (Edwards 2003, Fackenthal 2012, Trujillano 2015). The variant was also identified in dbSNP (ID: rs55816687) as “With Uncertain significance, other allele”, Clinvitae database (conflicting interpretations of pathogenicity), the ClinVar database (classified as benign by Invitae; classified as likely benign by GeneDx, Ambry Genetics, MMGLUM, Pathway Genomics; classified as uncertain significance by CSER_CC_NCGL, SCRP, BIC), the BIC database (10x with unknown clinical importance), UMD (28x with a “unclassified variant” classification) and Fanconi Anemia Mutation Database (LOVD). This variant was identified in the 1000 Genomes Project in 12 of 5000 chromosomes (frequency: 0.002), NHLBI GO Exome Sequencing Project in 19 of 4406 African American alleles, the Exome Aggregation Consortium database (August 8, 2016) in 61 of 120866 chromosomes (freq. 0.0005) in the following populations: African in 60 of 10122 chromosomes (freq. 0.006), Latino in 1 of 11476 chromosomes (freq. 0.0001), increasing the likelihood that this may be a low frequency benign variant in certain populations of origin. The p.Gln713 residue is not conserved in mammals and three out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and 5 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing; loss of splicing site at a non-splice site consensus sequence. However, this information is not predictive enough to assume pathogenicity. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as likely benign.
Clinical Genetics Laboratory, Department of Pathology,Netherlands Cancer Institute RCV000679159 SCV001905798 likely benign not provided no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000679159 SCV001930080 likely benign not provided no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000120312 SCV001959046 benign not specified no assertion criteria provided clinical testing

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