Variant chr16-88707120-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001012759.3(CTU2):c.69-16C>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 1,611,542 control chromosomes in the GnomAD database, including 56,187 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3650 hom., cov: 32)

Exomes 𝑓: 0.26 ( 52537 hom. )

Consequence

CTU2
NM_001012759.3 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.560

Variant links:

Genes affected

CTU2 (HGNC:28005): (cytosolic thiouridylase subunit 2) This gene encodes a protein which is involved in the post-transcriptional modification of transfer RNAs (tRNAs). The encoded protein plays a role in thiolation of uridine residue present at the wobble position in a subset of tRNAs, resulting in enhanced codon reading accuracy. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]

CTU2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 16-88707120-C-A is Benign according to our data. Variant chr16-88707120-C-A is described in ClinVar as [Benign]. Clinvar id is 1253335.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
CTU2	NM_001012759.3 linkuse as main transcript	c.69-16C>A	splice_polypyrimidine_tract_variant, intron_variant	ENST00000453996.7
CTU2	NM_001012762.3 linkuse as main transcript	c.69-16C>A	splice_polypyrimidine_tract_variant, intron_variant
CTU2	NM_001318507.2 linkuse as main transcript	c.69-16C>A	splice_polypyrimidine_tract_variant, intron_variant
CTU2	NM_001318513.2 linkuse as main transcript	c.-114-16C>A	splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTU2	ENST00000453996.7 linkuse as main transcript	c.69-16C>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001012759.3	P2	Q2VPK5-1

Frequencies

GnomAD3 genomes

AF:

0.194

AC:

29420

AN:

151992

Hom.:

3651

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0507

Gnomad AMI

AF:

0.209

Gnomad AMR

AF:

0.174

Gnomad ASJ

AF:

0.306

Gnomad EAS

AF:

0.0259

Gnomad SAS

AF:

0.252

Gnomad FIN

AF:

0.230

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.281

Gnomad OTH

AF:

0.219

GnomAD3 exomes

AF:

0.218

AC:

54667

AN:

250640

Hom.:

7242

AF XY:

0.230

AC XY:

31174

AN XY:

135696

show subpopulations

Gnomad AFR exome

AF:

0.0467

Gnomad AMR exome

AF:

0.117

Gnomad ASJ exome

AF:

0.304

Gnomad EAS exome

AF:

0.0258

Gnomad SAS exome

AF:

0.264

Gnomad FIN exome

AF:

0.238

Gnomad NFE exome

AF:

0.279

Gnomad OTH exome

AF:

0.247

GnomAD4 exome

AF:

0.260

AC:

378972

AN:

1459432

Hom.:

52537

Cov.:

AF XY:

0.262

AC XY:

190195

AN XY:

725804

show subpopulations

Gnomad4 AFR exome

AF:

0.0422

Gnomad4 AMR exome

AF:

0.124

Gnomad4 ASJ exome

AF:

0.303

Gnomad4 EAS exome

AF:

0.0169

Gnomad4 SAS exome

AF:

0.262

Gnomad4 FIN exome

AF:

0.239

Gnomad4 NFE exome

AF:

0.281

Gnomad4 OTH exome

AF:

0.244

GnomAD4 genome

AF:

0.193

AC:

29417

AN:

152110

Hom.:

3650

Cov.:

AF XY:

0.190

AC XY:

14149

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.0505

Gnomad4 AMR

AF:

0.174

Gnomad4 ASJ

AF:

0.306

Gnomad4 EAS

AF:

0.0257

Gnomad4 SAS

AF:

0.254

Gnomad4 FIN

AF:

0.230

Gnomad4 NFE

AF:

0.281

Gnomad4 OTH

AF:

0.217

Alfa

AF:

0.191

Hom.:

656

Bravo

AF:

0.181

Asia WGS

AF:

0.111

AC:

386

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 02, 2020	- -

CTU2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 27, 2023

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.1

DANN

Benign

0.70

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over