ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.7601C>T (p.Ala2534Val) (rs74047012)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000220233 SCV000273906 likely benign Hereditary cancer-predisposing syndrome 2015-09-02 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031691 SCV000147139 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Color RCV000220233 SCV000911016 benign Hereditary cancer-predisposing syndrome 2016-02-10 criteria provided, single submitter clinical testing
Counsyl RCV000031691 SCV000220346 likely benign Breast-ovarian cancer, familial 2 2014-05-22 criteria provided, single submitter literature only
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000045256 SCV000592127 likely benign not specified 2014-05-08 criteria provided, single submitter clinical testing
GeneDx RCV000045256 SCV000210430 likely benign not specified 2018-03-05 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 RCV000590175 SCV000695084 likely benign not provided 2017-01-19 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.7601C>T (p.Ala2534Val) variant, alternatively also known as 7829C>T, involves the alteration of a non-conserved nucleotide and is predicted as benign by 4/5 in silico tools. It is located in proximity to the exon-intron boundary (16 nucleotides away) and is predicted to create a cryptic donor site by 2/5 splice prediction tools. ESE finder predicts that this variant may cause loss of an ESE site. This variant was predicted to have uncertain significance by protein likelihood ratio model (Karchin_2008). However, these predictions have yet to be confirmed by functional studies. This variant was found in 12/120468 control chromosomes from ExAC at a frequency of 0.0000996, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503); however, it could still represent as a rare polymorphism. This variant has been reported in multiple breast and/or ovarian cancer patients in literature and clinical databases without strong evidence for pathogenicity. BIC and UMD each report a sample with this variant that also carries BRCA1 c.5263_5264insC (p.Ser1755?fs), strongly supporting for benign outcome (whether both databases reported the same individual is not known). One large case-control study did not find this variant as a significant risk allele (Haiman_2013). Clinical database/reputable databases in ClinVar have conflicting interpretation of this variant; it has been classified as variant of uncertain significance (3) as well as likely benign (3). Therefore, based on currently available lines of evidence, this variant is classified as "likely benign."
Invitae RCV000195379 SCV000073269 likely benign Hereditary breast and ovarian cancer syndrome 2018-01-05 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000590175 SCV000889135 likely benign not provided 2018-02-27 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031691 SCV000054298 likely benign Breast-ovarian cancer, familial 2 2011-02-04 no assertion criteria provided clinical testing
True Health Diagnostics RCV000220233 SCV000886675 likely benign Hereditary cancer-predisposing syndrome 2018-09-27 no assertion criteria provided clinical testing

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