ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.2256C>T (p.Asp752=) (rs766384913)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000587726 SCV000883487 likely benign not provided 2017-07-14 criteria provided, single submitter clinical testing The BRCA2 c.2256C>T;p.Asp752Asp variant has not been published in the medical literature or in gene-specific databases. The variant is listed in the HCI Breast Cancer Genes Prior Probabilities database as weak probability of pathogenicity. The variant is listed in the ClinVar database (Variation ID: 184350) and the dbSNP variant database (rs766384913) with an allele frequency of 0.001805 percent (5/277018 alleles) in the Genome Aggregation Database. The nucleotide at this position is weakly conserved across species and computational algorithms (SpliceSiteFinder-like, MaxEntScan, NNSplice, GeneSplicer, Human Splicing Finder) predict this variant does not have significant effect on splicing. Considering available information, this variant is classified as likely benign.
Ambry Genetics RCV000163583 SCV000214143 likely benign Hereditary cancer-predisposing syndrome 2014-11-12 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Synonymous alterations with insufficient evidence to classify as benign
Color RCV000163583 SCV000683474 likely benign Hereditary cancer-predisposing syndrome 2016-04-11 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000425141 SCV000591798 likely benign not specified 2015-08-31 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000495650 SCV000578683 likely benign Breast-ovarian cancer, familial 2 2017-06-29 reviewed by expert panel curation Synonymous substitution variant, with low bioinformatic likelihood to result in a splicing aberration (Splicing prior probability 0.02; http://priors.hci.utah.edu/PRIORS/).
GeneDx RCV000425141 SCV000512345 likely benign not specified 2017-05-19 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 RCV000587726 SCV000694599 uncertain significance not provided 2017-01-13 criteria provided, single submitter clinical testing Variant summary: The c.2256C>T variant involves the alteration of a non-conserved nucleotide and results in a synonymous change. Mutation taster predicts a neutral outcome for this change and 5/5 in silico tools via Alamut predict no significant impact on splicing sites. ESEfinder predicts a loss of binding motif for splicing enhancer. This variant is found in 3/121214 control chromosomes at a frequency of 0.0000247, which does not exceed maximal expected frequency of a pathogenic allele (0.0007503). The variant of interest has not, to our knowledge, been reported in affected individuals via publications; nor evaluated for functional impact by in vivo/vitro studies. Two clinical laboratories classified this variant as likely benign, without evidence to independently evaluate. Taken together, this variant was classified as VUS-possibly benign until more evidence becomes available.
Invitae RCV000203906 SCV000260825 likely benign Hereditary breast and ovarian cancer syndrome 2017-11-16 criteria provided, single submitter clinical testing

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