rs727502804

Positions:

• chr2-112756619-CT-C

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The ENST00000302450.11(CKAP2L):​c.751del​(p.Ser251AlafsTer6) variant causes a frameshift 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). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CKAP2L ENST00000302450.11 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.318

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]

ACMG classification

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 2-112756619-CT-C is Pathogenic according to our data. Variant chr2-112756619-CT-C is described in ClinVar as [Pathogenic]. Clinvar id is 162387.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-112756619-CT-C is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CKAP2L	NM_152515.5	c.751del	p.Ser251AlafsTer6	frameshift_variant	4/9	ENST00000302450.11	NP_689728.3
CKAP2L	NM_001304361.2	c.256del	p.Ser86AlafsTer6	frameshift_variant	4/9		NP_001291290.1
CKAP2L	XM_011510666.3	c.256del	p.Ser86AlafsTer6	frameshift_variant	3/8		XP_011508968.1
CKAP2L	NR_130712.2	n.489+273del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CKAP2L	ENST00000302450.11	c.751del	p.Ser251AlafsTer6	frameshift_variant	4/9	1	NM_152515.5	ENSP00000305204	P1
CKAP2L	ENST00000435431.5	c.478+273del		intron_variant, NMD_transcript_variant		2		ENSP00000414834

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Filippi syndrome Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 06, 2014

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs727502804; hg19: chr2-113514196;