ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5205A>G (p.Lys1735=) (rs1131692115)

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Total submissions: 3
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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) RCV000495582 SCV000578534 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/).
Integrated Genetics/Laboratory Corporation of America RCV000589764 SCV000694841 uncertain significance not provided 2017-06-12 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.5205A>G (p.Lys1735Lys) 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. 3/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant is absent in 119462 control chromosomes and has not, to our knowledge, been reported in affected individuals in the literature or clinical laboratories. Taken together, this variant is classified as VUS-possibly benign until additional evidence becomes available.
Invitae RCV000556553 SCV000635437 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-06-28 criteria provided, single submitter clinical testing This sequence change affects codon 1735 of the BRCA2 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the BRCA2 protein. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 427384). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this is a rare silent change with uncertain impact on splicing. It has been classified as a Variant of Uncertain Significance.

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