rs730882061
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_004523.4(KIF11):c.1039_1040del(p.Leu347GlufsTer8) variant causes a frameshift change involving the alteration of a conserved nucleotide. 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
KIF11
NM_004523.4 frameshift
NM_004523.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.76
Genes affected
KIF11 (HGNC:6388): (kinesin family member 11) This gene encodes a motor protein that belongs to the kinesin-like protein family. Members of this protein family are known to be involved in various kinds of spindle dynamics. The function of this gene product includes chromosome positioning, centrosome separation and establishing a bipolar spindle during cell mitosis. [provided by RefSeq, Jul 2008]
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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 10-92616740-ACT-A is Pathogenic according to our data. Variant chr10-92616740-ACT-A is described in ClinVar as [Pathogenic]. Clinvar id is 29769.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-92616740-ACT-A is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KIF11 | NM_004523.4 | c.1039_1040del | p.Leu347GlufsTer8 | frameshift_variant | 9/22 | ENST00000260731.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIF11 | ENST00000260731.5 | c.1039_1040del | p.Leu347GlufsTer8 | frameshift_variant | 9/22 | 1 | NM_004523.4 | 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
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jul 07, 2021 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 29769). This premature translational stop signal has been observed in individual(s) with clinical features of microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability (PMID: 22284827). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Leu347Glufs*8) in the KIF11 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in KIF11 are known to be pathogenic (PMID: 22284827, 24281367). - |
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Feb 01, 2022 | 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 (gnomAD); This variant is associated with the following publications: (PMID: 25996076, 32730767, 22284827) - |
Microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 10, 2012 | - - |
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