rs727502802
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Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The ENST00000302450.11(CKAP2L):c.571_572insA(p.Ile191AsnfsTer6) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,356 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Consequence
CKAP2L
ENST00000302450.11 frameshift
ENST00000302450.11 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.490
Genes affected
CKAP2L (HGNC:26877): (cytoskeleton associated protein 2 like) The protein encoded by this gene is thought to be a mitotic spindle protein important to neural stem or progenitor cells. Mutations in this gene have been associated with spindle organization defects, including mitotic spindle defects, lagging chromosomes, and chromatin bridges. There is evidence that mutations in this gene are associated with Filippi syndrome, characterized by growth defects, microcephaly, intellectual disability, facial feature defects, and syndactyly. There is a pseudogene of this gene on chromosome 20. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 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 2-112756799-A-AT is Pathogenic according to our data. Variant chr2-112756799-A-AT is described in ClinVar as [Pathogenic]. Clinvar id is 162384.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CKAP2L | NM_152515.5 | c.571_572insA | p.Ile191AsnfsTer6 | frameshift_variant | 4/9 | ENST00000302450.11 | NP_689728.3 | |
CKAP2L | NM_001304361.2 | c.76_77insA | p.Ile26AsnfsTer6 | frameshift_variant | 4/9 | NP_001291290.1 | ||
CKAP2L | XM_011510666.3 | c.76_77insA | p.Ile26AsnfsTer6 | frameshift_variant | 3/8 | XP_011508968.1 | ||
CKAP2L | NR_130712.2 | n.489+93_489+94insA | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CKAP2L | ENST00000302450.11 | c.571_572insA | p.Ile191AsnfsTer6 | frameshift_variant | 4/9 | 1 | NM_152515.5 | ENSP00000305204 | P1 | |
CKAP2L | ENST00000481732.5 | n.532_533insA | non_coding_transcript_exon_variant | 4/4 | 4 | |||||
CKAP2L | ENST00000435431.5 | c.478+93_478+94insA | intron_variant, NMD_transcript_variant | 2 | ENSP00000414834 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152238Hom.: 0 Cov.: 32
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152356Hom.: 0 Cov.: 32 AF XY: 0.0000268 AC XY: 2AN XY: 74506
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Filippi syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 06, 2014 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at