ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.2538A>C (p.Ser846=) (rs11571654)

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Total submissions: 17
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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) RCV000113057 SCV000578016 benign Breast-ovarian cancer, familial 2 2017-06-29 reviewed by expert panel curation Synonymous substitution variant, with low bioinformatic likelihood to alter mRNA splicing (splicing prior 0.02; http://priors.hci.utah.edu/PRIORS/) and frequency 0.0049 (South Asian), derived from ExAC (2014-12-17).
Invitae RCV000167797 SCV000072024 benign Hereditary breast and ovarian cancer syndrome 2018-01-04 criteria provided, single submitter clinical testing
GeneDx RCV000044011 SCV000167345 benign not specified 2014-02-12 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 RCV000162905 SCV000213392 likely benign Hereditary cancer-predisposing syndrome 2014-08-11 criteria provided, single submitter clinical testing
Counsyl RCV000113057 SCV000220710 likely benign Breast-ovarian cancer, familial 2 2014-09-19 criteria provided, single submitter literature only
Illumina Clinical Services Laboratory,Illumina RCV000167797 SCV000383653 likely benign Hereditary breast and ovarian cancer syndrome 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000378892 SCV000383654 likely benign Fanconi anemia 2016-06-14 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000167797 SCV000494432 benign Hereditary breast and ovarian cancer syndrome 2015-08-24 criteria provided, single submitter clinical testing Variant Summary: The variant of interest causes a synonymous change involving a non-conserved nucleotide with Mutation Taster predicting the variant to be a "polymorphism." 3/5 in silico programs via Alamut predict no significant effect on splicing and the removal of an ESE binding site, SRp40, although these predictions have yet to be functionally assessed. The variant of interest was observed in a large, broad control population, ExAC with an allele frequency of 98/120626 (1/1231, including 2 homozygotes), which exceeds the maximum expected allele frequency for a BRCA2 variant of 1/1333. The variant of interest has been reported in affected individuals via publications, including a reported co-occurrence with another pathogenic BRCA1 variant (5404delG; De Silva et al 2001). In addition, multiple reputable databases/clinical laboratories (BIC, GeneDx, Ambry Genetics, and Invitae) cite the variant with a classification of "likely benign/benign." Therefore, taking all available lines of evidence into consideration, the variant of interest is classified as benign.
Cancer Genetics and Genomics Laboratory,British Columbia Cancer Agency RCV000044011 SCV000586935 benign not specified 2017-04-18 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000044011 SCV000591809 benign not specified 2015-06-25 criteria provided, single submitter clinical testing
Color RCV000162905 SCV000683490 benign Hereditary cancer-predisposing syndrome 2015-12-28 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000113057 SCV000743274 benign Breast-ovarian cancer, familial 2 2014-10-10 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000113057 SCV000744427 likely benign Breast-ovarian cancer, familial 2 2015-09-21 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000044011 SCV000805674 benign not specified 2017-05-15 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000113057 SCV000146064 benign Breast-ovarian cancer, familial 2 2010-10-28 no assertion criteria provided clinical testing
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000656592 SCV000778653 likely benign not provided 2017-04-07 no assertion criteria provided clinical testing
True Health Diagnostics RCV000162905 SCV000805239 likely benign Hereditary cancer-predisposing syndrome 2018-05-09 no assertion criteria provided clinical testing

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