ClinVar Miner

Submissions for variant NM_000038.6(APC):c.1743+5C>T (rs876658386)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000222937 SCV000273526 uncertain significance Hereditary cancer-predisposing syndrome 2018-02-08 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
GeneDx RCV000482447 SCV000570045 uncertain significance not provided 2016-04-20 criteria provided, single submitter clinical testing This variant is denoted APC c.1743+5C>T or IVS14+5C>T and consists of a C>T nucleotide substitution at the +5 position of intron 14 of the APC gene. This variant is not predicted to cause abnormal splicing; 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 pathogenic or benign. APC c.1743+5C>T was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. The cytosine (C) nucleotide that is altered is conserved in mammals. Based on currently available information, it is unclear whether APC c.1743+5C>T is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000813144 SCV000953489 uncertain significance Familial adenomatous polyposis 1 2018-11-14 criteria provided, single submitter clinical testing This sequence change falls in intron 14 of the APC gene. It does not directly change the encoded amino acid sequence of the APC 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 APC-related disease. ClinVar contains an entry for this variant (Variation ID: 230099). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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