ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.1284A>G (p.Leu428=) (rs34770647)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000567193 SCV000661341 likely benign Hereditary cancer-predisposing syndrome 2016-07-27 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Synonymous alterations with insufficient evidence to classify as benign
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000495186 SCV000579014 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 RCV000443584 SCV000530775 likely benign not specified 2017-07-07 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 RCV000589808 SCV000694529 uncertain significance not provided 2017-05-15 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.1284A>G (p.Leu428Leu) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a benign outcome for this variant. 4/5 splice prediction tools predict no significant impact on normal splicing and ESE finder predicts that this variant does not affect ESE sites at the locus. However, these predictions have yet to be confirmed by functional studies. This variant was found in the large control database ExAC at a frequency of 0.0000166 (2/120480 control chromosomes), which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). In addition, one clinical diagnostic laboratory has classified this variant as likely benign. To our knowledge, the variant of interest has not been reported in affected individuals via publications, nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as VUS-possibly benign.
Invitae RCV000554913 SCV000635153 likely benign Hereditary breast and ovarian cancer syndrome 2017-11-29 criteria provided, single submitter clinical testing

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