rs6712572

Positions:

• chr2-112763101-G-T

Variant summary

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

The NM_152515.5(CKAP2L):​c.38-532C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 152,058 control chromosomes in the GnomAD database, including 29,413 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 0.60 (29413 hom., cov: 32)
• Consequence: CKAP2L NM_152515.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.628

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CKAP2L	NM_152515.5	c.38-532C>A		intron_variant		ENST00000302450.11
CKAP2L	NM_001304361.2	c.-399-532C>A		intron_variant
CKAP2L	XM_011510666.3	c.-392+1461C>A		intron_variant
CKAP2L	NR_130712.2	n.49-532C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CKAP2L	ENST00000302450.11	c.38-532C>A		intron_variant		1	NM_152515.5	P1

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90552 AN: 151940 Hom.: 29368 Cov.: 32

Gnomad AFR AF: 0.876

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.506

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.576

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

GnomAD4 genome AF: 0.596 AC: 90637 AN: 152058 Hom.: 29413 Cov.: 32 AF XY: 0.589 AC XY: 43773 AN XY: 74326

Gnomad4 AFR AF: 0.876

Gnomad4 AMR AF: 0.510

Gnomad4 ASJ AF: 0.506

Gnomad4 EAS AF: 0.307

Gnomad4 SAS AF: 0.535

Gnomad4 FIN AF: 0.439

Gnomad4 NFE AF: 0.502

Gnomad4 OTH AF: 0.570

Alfa AF: 0.561 Hom.: 3162

Bravo AF: 0.609

Asia WGS AF: 0.445 AC: 1548 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
DANN	Benign	0.39

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: rs6712572; hg19: chr2-113520678;