Variant rs1553442237 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PVS1PP5

The NM_152515.5(CKAP2L):c.157_485del(p.Thr53TyrfsTer6) variant causes a frameshift, splice region change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)

Consequence

CKAP2L
NM_152515.5 frameshift, splice_region

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]

CKAP2L links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 9 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

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
CKAP2L	NM_152515.5 linkuse as main transcript	c.157_485del	p.Thr53TyrfsTer6	frameshift_variant, splice_region_variant	4/9	ENST00000302450.11
CKAP2L	XM_011510666.3 linkuse as main transcript	c.-339_-11del		splice_region_variant, 5_prime_UTR_variant	3/8
CKAP2L	NM_001304361.2 linkuse as main transcript	c.-280-59_-11del		splice_acceptor_variant, 5_prime_UTR_variant, intron_variant	4/9
CKAP2L	NR_130712.2 linkuse as main transcript	n.168_489+7del		splice_donor_variant, splice_donor_5th_base_variant, non_coding_transcript_exon_variant, intron_variant	4/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CKAP2L	ENST00000302450.11 linkuse as main transcript	c.157_485del	p.Thr53TyrfsTer6	frameshift_variant, splice_region_variant	4/9	1	NM_152515.5	P1	Q8IYA6-1

Frequencies

GnomAD3 genomes

Cov.:

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

Cov.:

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

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.