2-112738945-C-G

Position:

• chr2-112738945-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152515.5(CKAP2L):​c.2116G>C​(p.Glu706Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E706D) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CKAP2L NM_152515.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.97

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]

NT5DC4 (HGNC:27678): (5'-nucleotidase domain containing 4) Predicted to enable 5'-nucleotidase activity. Predicted to be involved in dephosphorylation. [provided by Alliance of Genome Resources, Apr 2022]

NT5DC4 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3471169).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CKAP2L	NM_152515.5	c.2116G>C	p.Glu706Gln	missense_variant	9/9	ENST00000302450.11	NP_689728.3
NT5DC4	NM_001393655.1	c.*9C>G		3_prime_UTR_variant	17/17	ENST00000688554.1	NP_001380584.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CKAP2L	ENST00000302450.11	c.2116G>C	p.Glu706Gln	missense_variant	9/9	1	NM_152515.5	ENSP00000305204.6
NT5DC4	ENST00000688554.1	c.*9C>G		3_prime_UTR_variant	17/17		NM_001393655.1	ENSP00000509504.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 06, 2024

The c.2116G>C (p.E706Q) alteration is located in exon 9 (coding exon 9) of the CKAP2L gene. This alteration results from a G to C substitution at nucleotide position 2116, causing the glutamic acid (E) at amino acid position 706 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.072	T
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.7	M
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.14
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.018	D
Polyphen		1.0	D
Vest4		0.34
MutPred		0.31		Gain of MoRF binding (P = 0.1318);
MVP		0.44
MPC		0.35
ClinPred		0.89	D
GERP RS		5.5
Varity_R		0.16
gMVP		0.36

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-113496522;