2-112739474-T-G

Position:

• chr2-112739474-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152515.5(CKAP2L):​c.2013-426A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 152,060 control chromosomes in the GnomAD database, including 15,929 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.46 (15929 hom., cov: 32)
• Consequence: CKAP2L NM_152515.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.142

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CKAP2L	NM_152515.5	c.2013-426A>C		intron_variant		ENST00000302450.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CKAP2L	ENST00000302450.11	c.2013-426A>C		intron_variant		1	NM_152515.5	P1

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69551 AN: 151942 Hom.: 15927 Cov.: 32

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.446

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

GnomAD4 genome AF: 0.458 AC: 69572 AN: 152060 Hom.: 15929 Cov.: 32 AF XY: 0.455 AC XY: 33846 AN XY: 74334

Gnomad4 AFR AF: 0.497

Gnomad4 AMR AF: 0.437

Gnomad4 ASJ AF: 0.466

Gnomad4 EAS AF: 0.307

Gnomad4 SAS AF: 0.510

Gnomad4 FIN AF: 0.421

Gnomad4 NFE AF: 0.451

Gnomad4 OTH AF: 0.442

Alfa AF: 0.461 Hom.: 2401

Bravo AF: 0.454

Asia WGS AF: 0.417 AC: 1449 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.1
DANN	Benign	0.73

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: rs10165537; hg19: chr2-113497051;