chr2-112739377-T-A

Position:

• chr2-112739377-T-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_152515.5(CKAP2L):​c.2013-329A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0144 in 152,266 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.014 (31 hom., cov: 32)
• Consequence: CKAP2L NM_152515.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.901

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 2-112739377-T-A is Benign according to our data. Variant chr2-112739377-T-A is described in ClinVar as [Benign]. Clinvar id is 1183724.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0144 (2194/152266) while in subpopulation SAS AF= 0.0352 (170/4830). AF 95% confidence interval is 0.0309. There are 31 homozygotes in gnomad4. There are 1208 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 31 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CKAP2L	NM_152515.5	c.2013-329A>T		intron_variant		ENST00000302450.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CKAP2L	ENST00000302450.11	c.2013-329A>T		intron_variant		1	NM_152515.5	P1

Frequencies

GnomAD3 genomes AF: 0.0144 AC: 2197 AN: 152148 Hom.: 31 Cov.: 32

Gnomad AFR AF: 0.00263

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00838

Gnomad ASJ AF: 0.0202

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0356

Gnomad FIN AF: 0.0487

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0171

Gnomad OTH AF: 0.0139

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

GnomAD4 genome AF: 0.0144 AC: 2194 AN: 152266 Hom.: 31 Cov.: 32 AF XY: 0.0162 AC XY: 1208 AN XY: 74446

Gnomad4 AFR AF: 0.00262

Gnomad4 AMR AF: 0.00837

Gnomad4 ASJ AF: 0.0202

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0352

Gnomad4 FIN AF: 0.0487

Gnomad4 NFE AF: 0.0171

Gnomad4 OTH AF: 0.0137

Alfa AF: 0.0136 Hom.: 1

Bravo AF: 0.0105

Asia WGS AF: 0.0160 AC: 55 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.19
DANN	Benign	0.25

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: rs151168935; hg19: chr2-113496954;