ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.5070A>C (p.Lys1690Asn) (rs56087561)

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Total submissions: 22
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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) RCV000113374 SCV000244454 benign Breast-ovarian cancer, familial 2 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 = 0.0000000459
Invitae RCV000044548 SCV000072561 benign Hereditary breast and ovarian cancer syndrome 2020-12-04 criteria provided, single submitter clinical testing
GeneDx RCV000587449 SCV000108618 likely benign not provided 2020-10-09 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 21952622, 21702907, 11304778, 25948282, 22366370, 28324225, 21990134, 17924331, 17997147, 15172753, 18951446, 24212087, 24323938, 22811390, 12161607, 24489791, 26689913, 19912264, 24504028, 27930734, 18256760, 32444794)
Counsyl RCV000113374 SCV000154079 likely benign Breast-ovarian cancer, familial 2 2014-03-07 criteria provided, single submitter literature only
Michigan Medical Genetics Laboratories,University of Michigan RCV000113374 SCV000195987 likely benign Breast-ovarian cancer, familial 2 2014-11-03 criteria provided, single submitter clinical testing
Ambry Genetics RCV000162621 SCV000213056 benign Hereditary cancer-predisposing syndrome 2014-11-19 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.
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000768596 SCV000219345 likely benign Breast and/or ovarian cancer 2017-12-20 criteria provided, single submitter clinical testing
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia RCV000044548 SCV000257611 uncertain significance Hereditary breast and ovarian cancer syndrome 2015-04-17 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000074533 SCV000538493 uncertain significance not specified 2016-03-31 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: 24/65694 European; ClinVar: 3B/LB, 2 VUS
Cancer Genetics and Genomics Laboratory,British Columbia Cancer Agency RCV000074533 SCV000586957 benign not specified 2017-04-18 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000074533 SCV000593746 uncertain significance not specified 2016-12-08 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000074533 SCV000602858 benign not specified 2019-03-15 criteria provided, single submitter clinical testing
Color Health, Inc RCV000162621 SCV000683669 likely benign Hereditary cancer-predisposing syndrome 2015-04-23 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000587449 SCV000694825 benign not provided 2016-04-07 criteria provided, single submitter clinical testing Variant Summary: The c.5070A>C variant involves a conserved nucleotide in which 4/5 in silico tools predict a damaging outcome, and has a low prevalence in European controls (EVS: 2/8576 chrs and ExAC: 25/72,294 chrs). Though the observed allele frequency in general population is not higher than the maximal expected allele frequency for a BRCA2 pathogenic variant (1/1333) the presence of this variant in controls indicates that this variant might be a rare polymorphism. More importantly, the variant has been reported to co-occur with other deleterious variants in BRCA2 and BRCA1 (4 independent individuals who carry pathogenic variants in each BRCA1 and BRCA2, reported in UMD and BIC), strong evidence that this variantis benign. In addition, it has also been classified as benign by multiple reputable databases and clinical labs, databases and publications (Easton_2007, Lindor_2012 and Whiley_2014). There are no functional studies reported for the variant to date. Multifactorial probability based model also shows the variant to be benign. Taken together, this variant has been classified as Benign.
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000113374 SCV000743303 benign Breast-ovarian cancer, familial 2 2017-07-28 criteria provided, single submitter clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000113374 SCV000744461 benign Breast-ovarian cancer, familial 2 2017-05-31 criteria provided, single submitter clinical testing
Research and Development, ARUP Laboratories RCV001642358 SCV001854823 benign Breast-ovarian cancer, familial 2; Breast-ovarian cancer, familial 1; Hereditary breast and ovarian cancer syndrome 2020-01-20 criteria provided, single submitter curation
Breast Cancer Information Core (BIC) (BRCA2) RCV000113374 SCV000146529 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001353834 SCV000591937 benign Malignant tumor of breast no assertion criteria provided clinical testing Not expected to have clinical significance. myriad calls a polymorphism (personal communication). 39X in BIC (unknown clinical importance), 12X in UMD and co-occurred with a second pathogenic variant 5X increasing the likelihood the p.Lys1690Asn variant does not have clinical significance. Lindor_2012, Posterior probability of being deleterious = 1.94x10-7 - iarc working group calls class 1 - not pathogenic. Not well conserved in mammals but in-silico software (AlignGVGD, Polyphen-2, SIFT, BLOSUM) do not agree.
Mayo Clinic Laboratories, Mayo Clinic RCV000587449 SCV000778680 likely benign not provided 2017-10-16 no assertion criteria provided clinical testing
Clinical Genetics Laboratory, Department of Pathology,Netherlands Cancer Institute RCV000074533 SCV001905875 benign not specified no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000074533 SCV001956538 benign not specified no assertion criteria provided clinical testing

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