ClinVar Miner

Submissions for variant NM_000038.6(APC):c.646-8T>A (rs879254149)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000236430 SCV000293652 uncertain significance not specified 2017-04-18 criteria provided, single submitter clinical testing This variant is denoted APC c.646-8T>A or IVS6-8T>A and consists of a T>A nucleotide substitution at the -8 position of intron 6 of the APC gene. Multiple in silico models predict this variant to weaken the nearby natural acceptor 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.646-8T>A 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 thymine (T) nucleotide that is altered is not conserved across species. Based on currently available information, it is unclear whether APC c.646-8T>A is pathogenic or benign.
Invitae RCV000590396 SCV000562608 likely benign not provided 2019-01-14 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000590396 SCV000694094 uncertain significance not provided 2016-05-02 criteria provided, single submitter clinical testing Variant summary: The APC c.646-8T>A variant affects a conserved intronic nucleotide. Mutation Taster predicts a damaging outcome for this variant. 5/5 in silico tools via Alamut predict the variant to result in a mild weakening of a splice acceptor site (2.5-44%), however, the significance of these predictions has not been supported with functional studies. This variant was not found in 108080 control chromosomes. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical laboratories; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant was classified as a variant of uncertain significance (VUS) until additional information becomes available.
Color RCV000771392 SCV000903731 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-24 criteria provided, single submitter clinical testing

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