2-112738554-A-T

Position:

• chr2-112738554-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_152515.5(CKAP2L):​c.*269T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0148 in 420,428 control chromosomes in the GnomAD database, including 339 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.033 (277 hom., cov: 32)
  • Exomes 𝑓: 0.0046 (62 hom.)
• Consequence: CKAP2L NM_152515.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.282

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]

CKAP2L (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 2-112738554-A-T is Benign according to our data. Variant chr2-112738554-A-T is described in ClinVar as [Benign]. Clinvar id is 1225888.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CKAP2L	NM_152515.5	c.*269T>A		3_prime_UTR_variant	9/9	ENST00000302450.11	NP_689728.3
NT5DC4	NM_001393655.1	c.1345-359A>T		intron_variant		ENST00000688554.1	NP_001380584.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CKAP2L	ENST00000302450	c.*269T>A		3_prime_UTR_variant	9/9	1	NM_152515.5	ENSP00000305204.6
NT5DC4	ENST00000688554.1	c.1345-359A>T		intron_variant			NM_001393655.1	ENSP00000509504.1

Frequencies

GnomAD3 genomes AF: 0.0327 AC: 4977 AN: 152214 Hom.: 275 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0114

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.0224

GnomAD4 exome AF: 0.00457 AC: 1226 AN: 268096 Hom.: 62 Cov.: 0 AF XY: 0.00393 AC XY: 558 AN XY: 141894

Gnomad4 AFR exome AF: 0.110

Gnomad4 AMR exome AF: 0.00875

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00210

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000151

Gnomad4 OTH exome AF: 0.00876

GnomAD4 genome AF: 0.0328 AC: 4992 AN: 152332 Hom.: 277 Cov.: 32 AF XY: 0.0321 AC XY: 2394 AN XY: 74478

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.0114

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000828

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.0222

Alfa AF: 0.0266 Hom.: 27

Bravo AF: 0.0375

Asia WGS AF: 0.0100 AC: 37 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

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.40
DANN	Benign	0.71

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: rs1052529; hg19: chr2-113496131;