ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.4816A>G (p.Lys1606Glu) (rs80356943)

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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000048668 SCV000076681 benign not provided 2019-03-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV000130005 SCV000184830 uncertain significance Hereditary cancer-predisposing syndrome 2018-04-02 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000436368 SCV000219251 uncertain significance not specified 2017-07-28 criteria provided, single submitter clinical testing
GeneDx RCV000436368 SCV000512312 likely benign not specified 2017-02-09 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.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000436368 SCV000591540 uncertain significance not specified 2014-03-14 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000436368 SCV000605892 uncertain significance not specified 2016-12-21 criteria provided, single submitter clinical testing
Counsyl RCV000031193 SCV000785870 uncertain significance Breast-ovarian cancer, familial 1 2017-12-20 criteria provided, single submitter clinical testing
Color RCV000130005 SCV000903167 likely benign Hereditary cancer-predisposing syndrome 2017-03-22 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000436368 SCV000918792 likely benign not specified 2018-11-01 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.4816A>G (p.Lys1606Glu) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2.8e-05 in 246164 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.4816A>G has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer (Fitzgerald_1996, Judkins_2005, Simard_2007). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. Two independent publications spanning a decade report experimental evidence evaluating an impact on protein function, both of which demonstrate no functional impact of this variant on measures of yeast small colony phenotype assay (Coyne 2004) and a transcriptional activation assay coupled to a Bayesian hierarchical model that estimated the likelihood of pathogenicity (Woods, 2016). Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments (4 VUS, 2 likely benign/benign). Taken together, the emerging functional evidence surrounding this variant published in reputed recently published journals and recent classifications in data sharing databases (ClinVar) support the move towards a benign impact for this variant. However, additional evidence supporting presence in unaffected controls (due to its rarity), lack of co-seggregation with disease, and co-occurrences with other pathological variants in BRCA1 is awaited. Based on the evidence outlined above, the variant was classified as likely benign.
Mendelics RCV000031193 SCV001140508 benign Breast-ovarian cancer, familial 1 2019-05-28 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031193 SCV000053793 likely benign Breast-ovarian cancer, familial 1 2012-05-01 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000031193 SCV000145189 uncertain significance Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735492 SCV000863630 uncertain significance Breast and/or ovarian cancer no assertion criteria provided clinical testing

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