rs1064794330
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_013275.6(ANKRD11):c.3224_3227del(p.Glu1075GlyfsTer242) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
ANKRD11
NM_013275.6 frameshift
NM_013275.6 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.74
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 16-89283314-CCTTT-C is Pathogenic according to our data. Variant chr16-89283314-CCTTT-C is described in ClinVar as [Pathogenic]. Clinvar id is 420179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ANKRD11 | NM_013275.6 | c.3224_3227del | p.Glu1075GlyfsTer242 | frameshift_variant | 9/13 | ENST00000301030.10 | NP_037407.4 | |
ANKRD11 | NM_001256182.2 | c.3224_3227del | p.Glu1075GlyfsTer242 | frameshift_variant | 10/14 | NP_001243111.1 | ||
ANKRD11 | NM_001256183.2 | c.3224_3227del | p.Glu1075GlyfsTer242 | frameshift_variant | 9/13 | NP_001243112.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ANKRD11 | ENST00000301030.10 | c.3224_3227del | p.Glu1075GlyfsTer242 | frameshift_variant | 9/13 | 5 | NM_013275.6 | ENSP00000301030 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
KBG syndrome Pathogenic:5
Pathogenic, no assertion criteria provided | clinical testing | Autoinflammatory diseases unit, CHU de Montpellier | Jan 21, 2019 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Genome Medicine, Institute for Basic Research in Developmental Disabilities | - | KBG syndrome - |
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Sep 01, 2017 | This frameshift mutation is categorized as deleterious according to ACMG guidelines (PMID:18414213). It was found once in our laboratory in an 8-year-old female with bipolar, PDD, ADHD, failure to thrive, leg length discrepancy, spondylolisthesis, dysmorphic features. Inherited from mother with psychiatric issues. - |
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 15, 2023 | This sequence change creates a premature translational stop signal (p.Glu1075Glyfs*242) 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 (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with KBG syndrome (PMID: 28250421, 29453417). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 420179). For these reasons, this variant has been classified as Pathogenic. - |
Pathogenic, criteria provided, single submitter | clinical testing | Institute of Human Genetics, University of Leipzig Medical Center | Sep 10, 2019 | This variant was identified as de novo (maternity and paternity confirmed). - |
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Dec 07, 2021 | Frameshift 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; Not observed at significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 29258554, 28250421, 29453417, 25326635, 32476269) - |
Pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2022 | ANKRD11: PVS1, PM2 - |
Computational scores
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at