ClinVar Miner

Submissions for variant NM_000136.3(FANCC):c.843+5G>A (rs369082921)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000200370 SCV000254265 uncertain significance Fanconi anemia 2018-11-06 criteria provided, single submitter clinical testing This sequence change falls in intron 8 of the FANCC gene. It does not directly change the encoded amino acid sequence of the FANCC protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs369082921, ExAC 0.01%) but has not been reported in the literature in individuals with a FANCC-related disease. ClinVar contains an entry for this variant (Variant ID: 216291). Nucleotide substitutions at the +5 position of the intron are relatively common causes of aberrant splicing (PMID: 17576681). Algorithms developed to predict the effect of nucleotide changes on mRNA splicing suggest that this variant may alter mRNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this is a rare intronic change with uncertain impact on splicing. It has been classified as a Variant of Uncertain Significance.
GeneDx RCV000486099 SCV000566528 uncertain significance not provided 2018-10-08 criteria provided, single submitter clinical testing This variant is denoted FANCC c.843+5G>A or IVS8+5G>A and consists of a G>A nucleotide substitution at the +5 position of intron 8 of the FANCC gene. In silico analyses, which include splice predictors and evolutionary conservation, supports a deleterious effect; however, in the absence of RNA or functional studies, the actual effect of this variant is unknown. This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. FANCC c.843+5G>A was not observed at a significant allele frequency in large population cohorts (Lek 2016). Based on currently available evidence, it is unclear whether FANCC c.843+5G>A is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Counsyl RCV000666113 SCV000790355 uncertain significance Fanconi anemia, complementation group C 2017-03-16 criteria provided, single submitter clinical testing
Mendelics RCV000666113 SCV000838349 uncertain significance Fanconi anemia, complementation group C 2018-07-02 criteria provided, single submitter clinical testing

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