Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000481036 | SCV000570849 | uncertain significance | not provided | 2016-07-01 | criteria provided, single submitter | clinical testing | This variant is denoted APC c.1626+3A>C or IVS13+3A>C and consists of a A>C nucleotide substitution at the +3 position of intron 13 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. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. APC c.1626+3A>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 adenine (A) nucleotide that is altered is conserved across species. Based on currently available information, it is unclear whether APC c.1626+3A>C is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. |
Ambry Genetics | RCV000491874 | SCV000579820 | uncertain significance | Hereditary cancer-predisposing syndrome | 2014-05-28 | criteria provided, single submitter | clinical testing | The c.1626+3A>C intronic variant results from an A to C substitution 3 nucleotides after coding exon 12 in the APC gene. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. To date, this alteration has been detected with an allele frequency of approximately 0.01% (greater than 9500 alleles tested) in our clinical cohort (includes this individual). This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native donor splice site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of c.1626+3A>C remains unclear. |