GeneBe

rs1553442237

Positions:

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5

The NM_001304361.2(CKAP2L):​c.-280-59_-11del variant causes a splice acceptor, splice region, 5 prime UTR, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

CKAP2L
NM_001304361.2 splice_acceptor, splice_region, 5_prime_UTR, intron

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 1.92
Variant links:
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 Likely_pathogenic. Variant got 7 ACMG points.

PVS1
Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.6758462 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 2-112756885-ACATTTACCATTTCCTTGATCTGTTAACTGCTGCTTTGTAGTTTTCAATTGCTCTATATTAAGTGACCCCACAGGTTTTCTTGACAGTTCTCCTGTTGTGGACGATCCAGCTTCACACTGTTGAAAACTCTTGCTAGAAGGCTTAGAGTATGGGTTAGAAGAAACACATTCTGAAGTCAGCCTTTTGCCCAGAAGTTTTGGTGGCTCCAACTTCGGCTTCTGGGACCCTGCAGTATTAGGTGGTCTGGGCTGGAGTTTAATGCTGATGGACCTTTTAGGTTTGACAGGCAAAACAACATGGTTGGTAACATCATTTTTGGGTCTAATAGT-A is Pathogenic according to our data. Variant chr2-112756885-ACATTTACCATTTCCTTGATCTGTTAACTGCTGCTTTGTAGTTTTCAATTGCTCTATATTAAGTGACCCCACAGGTTTTCTTGACAGTTCTCCTGTTGTGGACGATCCAGCTTCACACTGTTGAAAACTCTTGCTAGAAGGCTTAGAGTATGGGTTAGAAGAAACACATTCTGAAGTCAGCCTTTTGCCCAGAAGTTTTGGTGGCTCCAACTTCGGCTTCTGGGACCCTGCAGTATTAGGTGGTCTGGGCTGGAGTTTAATGCTGATGGACCTTTTAGGTTTGACAGGCAAAACAACATGGTTGGTAACATCATTTTTGGGTCTAATAGT-A is described in ClinVar as [Pathogenic]. Clinvar id is 162388.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-112756885-ACATTTACCATTTCCTTGATCTGTTAACTGCTGCTTTGTAGTTTTCAATTGCTCTATATTAAGTGACCCCACAGGTTTTCTTGACAGTTCTCCTGTTGTGGACGATCCAGCTTCACACTGTTGAAAACTCTTGCTAGAAGGCTTAGAGTATGGGTTAGAAGAAACACATTCTGAAGTCAGCCTTTTGCCCAGAAGTTTTGGTGGCTCCAACTTCGGCTTCTGGGACCCTGCAGTATTAGGTGGTCTGGGCTGGAGTTTAATGCTGATGGACCTTTTAGGTTTGACAGGCAAAACAACATGGTTGGTAACATCATTTTTGGGTCTAATAGT-A is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CKAP2LNM_152515.5 linkuse as main transcriptc.157_485del p.Thr53fs frameshift_variant, splice_region_variant 4/9 ENST00000302450.11 NP_689728.3 Q8IYA6-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CKAP2LENST00000302450.11 linkuse as main transcriptc.157_485del p.Thr53fs frameshift_variant, splice_region_variant 4/91 NM_152515.5 ENSP00000305204.6 Q8IYA6-1

Frequencies

GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
Cov.:
32

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 providedliterature onlyOMIMNov 06, 2014- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1553442237; hg19: chr2-113514462; API