ClinVar Miner

Submissions for variant NM_000038.6(APC):c.1408+3A>G (rs534358523)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000550150 SCV000647174 uncertain significance Familial adenomatous polyposis 1 2019-12-15 criteria provided, single submitter clinical testing This sequence change falls in intron 11 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 (rs534358523, ExAC 0.03%). This variant has not been reported in the literature in individuals with APC-related disease. ClinVar contains an entry for this variant (Variation ID: 469705). 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 disrupt the consensus 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.
Ambry Genetics RCV000567805 SCV000667397 likely benign Hereditary cancer-predisposing syndrome 2019-09-05 criteria provided, single submitter clinical testing In silico models in agreement (benign);Other data supporting benign classification;RNA Studies
Color Health, Inc RCV000567805 SCV000909245 uncertain significance Hereditary cancer-predisposing syndrome 2020-10-13 criteria provided, single submitter clinical testing This variant causes an A to G nucleotide substitution at the +3 position of intron 11 of the APC gene. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 8/248924 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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