rs1555529181
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_013275.6(ANKRD11):c.2404_2407del(p.Leu802LysfsTer60) 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: 5.01
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 16-89284134-TTGAG-T is Pathogenic according to our data. Variant chr16-89284134-TTGAG-T is described in ClinVar as [Pathogenic]. Clinvar id is 547949.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANKRD11 | NM_013275.6 | c.2404_2407del | p.Leu802LysfsTer60 | frameshift_variant | 9/13 | ENST00000301030.10 | |
ANKRD11 | NM_001256182.2 | c.2404_2407del | p.Leu802LysfsTer60 | frameshift_variant | 10/14 | ||
ANKRD11 | NM_001256183.2 | c.2404_2407del | p.Leu802LysfsTer60 | frameshift_variant | 9/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANKRD11 | ENST00000301030.10 | c.2404_2407del | p.Leu802LysfsTer60 | frameshift_variant | 9/13 | 5 | NM_013275.6 | 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:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
KBG syndrome Pathogenic:3
Pathogenic, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Mar 16, 2017 | - - |
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 | Illumina Laboratory Services, Illumina | Dec 21, 2022 | The ANKRD11 c.2404_2407del (p.Leu802LysfsTer60) variant results in the deletion of four nucleotides at position c. 2404-2407, causing a shift in the protein reading frame that is predicted to result in premature termination of the protein. Loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay is expected. This variant has been reported in one affected individual in a de novo state, however clinical details were not specified (PMID: 33144682). This variant is not found 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.2404_2407del (p.Leu802LysfsTer60) variant is classified pathogenic for KBG syndrome. - |
Computational scores
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Calibrated prediction
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Prediction
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