ClinVar Miner

Submissions for variant NM_000038.6(APC):c.1312+5G>C (rs886039507)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000254697 SCV000322200 likely pathogenic not provided 2016-05-12 criteria provided, single submitter clinical testing This variant is denoted APC c.1312+5G>C or IVS10+5G>C and consists of a G>C nucleotide substitution at the +5 position of intron 10 of the APC gene. Multiple in silico models predict this variant to destroy the nearby natural donor site and to possibly cause abnormal gene splicing; however, in the absence of RNA or functional studies, the actual effect of this variant is unknown. Importantly, two other variants impacting the same nucleotide, APC c.1312+5G>A and c.1312+5G>T, have both been shown in RNA based assays to result in skipping of exon 10, also published as exon 9, resulting in a frameshift and a subsequent premature stop codon (Mihalatos 2005, Varesco 1994). This variant, APC c.1312+5G>C, has been observed in one individual undergoing APC testing at a clinical laboratory (Kerr 2013). APC c.1312+5G>C 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 guanine (G) nucleotide that is altered is conserved across species. Based on the currently available information, we consider APC c.1312+5G>C to be a likely pathogenic variant.

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