ClinVar Miner

Submissions for variant NM_000038.6(APC):c.1743+6T>C (rs766973462)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000433034 SCV000520203 likely benign not specified 2016-11-01 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.
Invitae RCV000461002 SCV000552664 uncertain significance Familial adenomatous polyposis 1 2018-12-27 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 present in population databases (rs766973462, ExAC 0.01%). This variant has not been reported in the literature in individuals with APC-related disease. ClinVar contains an entry for this variant (Variation ID: 381126). 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.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000433034 SCV000966577 uncertain significance not specified 2018-09-07 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The c.1743+6T>C var iant in APC has not been reported in the literature, but has been reported in Cl inVar as VUS and Likely Benign (Variation ID 381126). It was also identified in 1/111552 European chromosomes by the Genome Aggregation Database (gnomAD, http:/ /gnomad.broadinstitute.org). This variant is located in the 5' splice region. Co mputational tools do not suggest an impact to splicing; however, this informatio n is not predictive enough to rule out pathogenicity. In summary, while the clin ical significance of the c.1743+6T>C variant is uncertain, its location and the predicted lack of splice site impact suggests that it is more likely to be benig n. ACMG/AMP criteria applied: PM2, BP4.

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