rs886041791
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_013275.6(ANKRD11):c.2197C>T(p.Arg733Ter) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
ANKRD11
NM_013275.6 stop_gained
NM_013275.6 stop_gained
Scores
2
4
1
Clinical Significance
Conservation
PhyloP100: 4.14
Genes affected
ANKRD11 (HGNC:21316): (ankyrin repeat domain containing 11) This locus encodes an ankryin repeat domain-containing protein. The encoded protein inhibits ligand-dependent activation of transcription. Mutations in this gene have been associated with KBG syndrome, which is characterized by macrodontia, distinctive craniofacial features, short stature, skeletal anomalies, global developmental delay, seizures and intellectual disability. Alternatively spliced transcript variants have been described. Related pseudogenes exist on chromosomes 2 and X. [provided by RefSeq, Jan 2012]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 18 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 16-89284345-G-A is Pathogenic according to our data. Variant chr16-89284345-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 280620.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-89284345-G-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANKRD11 | NM_013275.6 | c.2197C>T | p.Arg733Ter | stop_gained | 9/13 | ENST00000301030.10 | |
ANKRD11 | NM_001256182.2 | c.2197C>T | p.Arg733Ter | stop_gained | 10/14 | ||
ANKRD11 | NM_001256183.2 | c.2197C>T | p.Arg733Ter | stop_gained | 9/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANKRD11 | ENST00000301030.10 | c.2197C>T | p.Arg733Ter | stop_gained | 9/13 | 5 | NM_013275.6 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 38
GnomAD4 exome
Cov.:
38
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
KBG syndrome Pathogenic:3
Likely pathogenic, criteria provided, single submitter | research | HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology | Mar 09, 2017 | - - |
Pathogenic, criteria provided, single submitter | research | Medical Cytogenetics and Molecular Genetics Laboratory, IRCCS Istituto Auxologico Italiano | Nov 01, 2021 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | May 26, 2023 | The ANKRD11 c.2197C>T (p.Arg733Ter) nonsense variant is predicted to result in the loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in a de novo state in the literature in individuals with KBG syndrome (PMID: 31191201, 32124548, 34971082, 35682590). This variant is not observed in version 2.1.1 or version 3.1.2 of the Genome Aggregation Database. This variant was identified in a de novo state. Based on the available evidence, the c.2197C>T (p.Arg733Ter) variant is classified as pathogenic for KBG syndrome. - |
not provided Pathogenic:3
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Jan 15, 2021 | Not observed in large population cohorts (Lek et al., 2016); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 32124548, 31191201) - |
Pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2023 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Laboratoire Génétique Moléculaire, CHRU TOURS | Jan 14, 2019 | - - |
Inborn genetic diseases Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 12, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A;A
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at