Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
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, |
RCV001261293 | SCV002574859 | pathogenic | KBG syndrome | 2022-09-22 | criteria provided, single submitter | clinical testing | |
Preventiongenetics, |
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, |
RCV001261293 | SCV001438102 | pathogenic | KBG syndrome | 2019-06-12 | no assertion criteria provided | clinical testing |