ClinVar Miner

Submissions for variant NM_000038.6(APC):c.8441_8444del (p.Lys2814fs) (rs879253985)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000589432 SCV000293072 uncertain significance not provided 2017-06-26 criteria provided, single submitter clinical testing This deletion of four nucleotides in APC is denoted c.8441_8444delAGAA at the cDNA level and p.Lys2814SerfsX26 (K2814SfsX26) at the protein level. The normal sequence, with the bases that are deleted in brackets, is ACAA[delAGAA]GCGA. The deletion causes a frameshift which changes a Lysine to a Serine at codon 2814, and creates a premature stop codon at position 26 of the new reading frame. As this deletion is in the last exon, nonsense mediated decay is not expected to occur. Although this variant has not, to our knowledge, been reported in the literature, it might cause loss of normal protein function through protein truncation. Based on currently available information, it is unclear whether this deletion is a pathogenic variant or a benign variant. We consider it to be a variant of uncertain significance.
Color RCV000581107 SCV000681929 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-14 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000589432 SCV000694145 uncertain significance not provided 2016-04-25 criteria provided, single submitter clinical testing Variant summary: The c.8441_8444delAGAA (p.Lys2814Serfs) variant results in a premature termination codon, predicted to cause a truncated protein, which is a commonly known mechanism for disease. However, the variant affects an amino acid that is located 29 amino acids from the end of the protein coding region of the gene, and creates a premature termination 26 amino acids downstream, therefore the effect of this variant may be reduced considering its location. The variant was observed in the large and broad cohorts of the ExAC project at an allele frequency of 0.0008% which does not exceed the maximal expected allele frequency for a pathogenic variant in APC (0.006%). 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.

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