ClinVar Miner

Submissions for variant NM_013275.6(ANKRD11):c.3704_3707del (p.Lys1235fs)

dbSNP: rs1555528354
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000627445 SCV000748445 pathogenic not provided 2018-03-13 criteria provided, single submitter clinical testing The c.3704_3707delAACA variant in the ANKRD11 gene has been reported previously in association with KBG syndrome (Low et al., 2016). The c.3704_3707delAACA variant causes a frameshift starting with codon Lysine 1235, changes this amino acid to an Arginine residue, and creates a premature Stop codon at position 82 of the new reading frame, denoted p.Lys1235ArgfsX82. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.3704_3707delAACA variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.3704_3707delAACA as a pathogenic variant.
Baylor Genetics RCV001261293 SCV001519855 pathogenic KBG syndrome 2019-02-20 criteria provided, single submitter clinical testing This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. This variant has been previously reported as disease-causing [PMID 27667800, 25533962]
Invitae RCV001261293 SCV002232213 pathogenic KBG syndrome 2021-06-26 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys1235Argfs*82) in the ANKRD11 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ANKRD11 are known to be pathogenic (PMID: 21782149, 25125236, 25413698, 25652421). This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of KBG syndrome (PMID: 27667800). ClinVar contains an entry for this variant (Variation ID: 523956). For these reasons, this variant has been classified as Pathogenic.
Institute for Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin RCV001261293 SCV002574859 pathogenic KBG syndrome 2022-09-22 criteria provided, single submitter clinical testing
Preventiongenetics, part of Exact Sciences RCV003411482 SCV004108990 pathogenic ANKRD11-related condition 2023-04-14 criteria provided, single submitter clinical testing The ANKRD11 c.3704_3707delAACA variant is predicted to result in a frameshift and premature protein termination (p.Lys1235Argfs*82). This variant has been reported in at least two individuals with KBG syndrome, and in one individual was determined to be de novo (Table S4, Deciphering Developmental Disorders Study. 2015. PubMed ID: 25533962; Table 2, Martinez-Cayuelas E et al. 2022. PMID: 36446582). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Frameshift variants in ANKRD11 are expected to be pathogenic. This variant is interpreted as pathogenic.
Autoinflammatory diseases unit, CHU de Montpellier RCV001261293 SCV001438102 pathogenic KBG syndrome 2019-06-12 no assertion criteria provided clinical testing

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