ClinVar Miner

Submissions for variant NM_013275.6(ANKRD11):c.2409_2412del (p.Glu805fs) (rs886039902)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000489189 SCV000577395 pathogenic not provided 2017-03-31 criteria provided, single submitter clinical testing The c.2409_2412delAAAA variant in the ANKRD11 gene has not been reported previously as apathogenic variant nor as a benign variant, to our knowledge. The ANKRD11 variant causes aframeshift starting with codon Glutamic acid 805, changes this amino acid to an Arginine residue, andcreates a premature Stop codon at position 57 of the new reading frame, denoted p.Glu805ArgfsX57.This variant is predicted to cause loss of normal protein function either through protein truncation ornonsense-mediated mRNA decay. The c.2409_2412delAAAA variant is not observed in largepopulation cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server).We interpret c.2409_2412delAAAA as a pathogenic variant.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000826156 SCV000967692 likely pathogenic KBG syndrome 2016-09-02 criteria provided, single submitter clinical testing The p.Glu805Argfs*57 variant in ANKRD11 has not been reported in patients and is absent from large population studies, though the ability of these studies to ac curately detect indels may be limited. This variant is predicted to cause a fram eshift, which alters the protein?s amino acid sequence beginning at position 805 and leads to a premature termination codon 57 amino acids downstream. This alte ration is then predicted to lead to a truncated or absent protein. Heterozygous loss of function of function of the ANKRD11 gene is an established disease mecha nism in KBG syndrome. In summary, the p.Glu805Argfs*57 variant in ANKRD11 meets criteria to be classified as likely pathogenic for KBG syndrome in an autosomal dominant manner based on predicted impact to the protein.

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