ClinVar Miner

Submissions for variant NM_000038.6(APC):c.1626+4C>A (rs1202435147)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color RCV000583572 SCV000686845 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-11 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000590026 SCV000694002 uncertain significance not provided 2017-04-27 criteria provided, single submitter clinical testing Variant summary: The APC c.1626+4C>A variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a damaging 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. The variant of interest is absent in a large, broad control population, ExAC in 117720 control chromosomes. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. This variant is co-occurring with a likely pathogenic variant in this sample (MSH6 c.3261dupC; p.Phe1088fsX5). Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available.
Invitae RCV000646345 SCV000768113 uncertain significance Familial adenomatous polyposis 1 2018-12-26 criteria provided, single submitter clinical testing This sequence change falls in intron 13 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. 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 may create or strengthen a splice site, 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000590026 SCV000888721 uncertain significance not provided 2017-10-30 criteria provided, single submitter clinical testing
GeneDx RCV000590026 SCV000969799 likely benign not provided 2018-05-25 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.

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