ClinVar Miner

Submissions for variant NM_000038.6(APC):c.645+1G>A (rs863225370)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000231167 SCV000282796 pathogenic Familial adenomatous polyposis 1 2019-01-11 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 6 of the APC gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). Disruption of this splice site has been observed in individuals affected with familial adenomatous polyposis (PMID: 8381580, 20685668, 17411426, 22987206). ClinVar contains an entry for this variant (Variation ID: 218000). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in APC are known to be pathogenic (PMID: 17963004, 20685668). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000202059 SCV000322199 likely pathogenic not provided 2017-04-27 criteria provided, single submitter clinical testing This variant is denoted APC c.645+1G>A or IVS6+1G>A and consists of a G>A nucleotide substitution at the +1 position of intron 6 of the APC gene. This variant destroys a canonical splice donor site and is predicted to cause abnormal gene splicing, leading to either an abnormal message that is subject to nonsense-mediated mRNA decay or to an abnormal protein product. This variant has been reported in individuals with a history of familial adenomatous polyposis (Olschwang 1993, Lagarde 2010). Based on the currently available information, we consider APC c.645+1G>A to be a likely pathogenic variant.
Ambry Genetics RCV001025281 SCV001187442 pathogenic Hereditary cancer-predisposing syndrome 2019-03-18 criteria provided, single submitter clinical testing Alterations at the canonical donor/acceptor sites (+/- 1, 2) without other strong (b-level) evidence supporting pathogenicity;Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation;Well-characterized mutation at same position
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000202059 SCV000257024 pathogenic not provided no assertion criteria provided research

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