ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.966-3C>T (rs1064796091)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color RCV000775948 SCV000910452 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-10 criteria provided, single submitter clinical testing
GeneDx RCV000484457 SCV000572516 uncertain significance not provided 2018-03-26 criteria provided, single submitter clinical testing This variant is denoted RAD51C c.966-3C>T or IVS7-3C>T and consists of a C>T nucleotide substitution at the -3 position of intron 7 of the RAD51C gene. In-silico analysis, which includes splice predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. RAD51C c.966-3C>T was not observed in large population cohorts (Lek 2016). Based on currently available information, it is unclear whether RAD51C c.966-3C>T is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000576273 SCV000676966 uncertain significance Fanconi anemia, complementation group O 2017-06-26 criteria provided, single submitter clinical testing This sequence change falls in intron 7 of the RAD51C gene. It does not directly change the encoded amino acid sequence of the RAD51C protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with a RAD51C-related disease. ClinVar contains an entry for this variant (Variation ID: 422917). Nucleotide substitutions within the consensus splice site are relatively common causes of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, this variant has uncertain impact on RAD51C function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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