ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.3858_3860del (p.Lys1286del) (rs80359406)

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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000859082 SCV000072298 benign not provided 2019-02-26 criteria provided, single submitter clinical testing
Ambry Genetics RCV000131324 SCV000186297 likely benign Hereditary cancer-predisposing syndrome 2017-09-11 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: No disease association in small case-control study,Co-occurence with mutation in same gene (phase unknown)
GeneDx RCV000044285 SCV000210598 likely benign not specified 2017-12-13 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.
Integrated Genetics/Laboratory Corporation of America RCV000200063 SCV000494412 uncertain significance Hereditary breast and ovarian cancer syndrome 2016-04-01 criteria provided, single submitter clinical testing Variant Summary: The variant of interest causes an in-frame deletion. The variant of interest was found in 10/89936 control chromosomes (1/9090), which does not exceed the predicted maximum expected allele frequency for a pathogenic BRCA2 variant of 1/1333. The variant of interest has been reported in affected individuals via publications, although with limited information (ie lack of co-segregation and co-occurrence data). Multiple reputable clinical laboratories/databases cite the variant with conflicting classifications "pathogenic/uncertain significance/likely benign." Therefore, taking all available lines of evidence into consideration, the variant of interest is classified as a "Variant of Uncertain Significance (VUS)," until additional information becomes available.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000044285 SCV000591879 uncertain significance not specified 2012-06-26 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000859082 SCV000600566 likely benign not provided 2019-07-03 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000044285 SCV000602823 likely benign not specified 2016-11-17 criteria provided, single submitter clinical testing
Color RCV000131324 SCV000683585 likely benign Hereditary cancer-predisposing syndrome 2015-09-21 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000044285 SCV000694725 likely benign not specified 2019-04-27 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.3858_3860delAAA (p.Lys1286del) results in an in-frame deletion that is predicted to remove one amino acid from the encoded protein. The variant allele was found at a frequency of 9.2e-05 in 195742 control chromosomes, predominantly at a frequency of 0.00089 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 1.19 fold of the estimated maximal expected allele frequency for a pathogenic variant in BRCA2 causing Hereditary Breast and Ovarian Cancer phenotype (0.00075), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. c.3858_3860delAAA has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer. These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer (Malone_2000, Fernandes_2016). To our knowledge, no publications report experimental evidence evaluating an impact on protein function. Seven clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
Mendelics RCV000200063 SCV000838790 likely benign Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Mendelics RCV000031442 SCV001139075 likely benign Breast-ovarian cancer, familial 2 2019-05-28 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031442 SCV000054047 benign Breast-ovarian cancer, familial 2 2009-09-25 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031442 SCV000146313 uncertain significance Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing

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