16-88707120-C-A

Variant names:

• chr16-88707120-C-A
• rs11641194
• NM_001012759.3:c.69-16C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001012759.3(CTU2):​c.69-16C>A variant causes a 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 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.560
• Publications: 14 publications found

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 Gene-Disease associations (from GenCC):

• microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTU2	NM_001012759.3	c.69-16C>A		intron_variant	Intron 1 of 14	ENST00000453996.7	NP_001012777.1
CTU2	NM_001318507.2	c.69-16C>A		intron_variant	Intron 1 of 14		NP_001305436.1
CTU2	NM_001012762.3	c.69-16C>A		intron_variant	Intron 1 of 13		NP_001012780.1
CTU2	NM_001318513.2	c.-114-16C>A		intron_variant	Intron 1 of 13		NP_001305442.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTU2	ENST00000453996.7	c.69-16C>A		intron_variant	Intron 1 of 14	1	NM_001012759.3	ENSP00000388320.2

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29420 AN: 151992 Hom.: 3651 Cov.: 32

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

GnomAD2 exomes AF: 0.218 AC: 54667 AN: 250640 AF XY: 0.230

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 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.: 32 AF XY: 0.262 AC XY: 190195 AN XY: 725804

African (AFR) AF: 0.0422 AC: 1410 AN: 33448

American (AMR) AF: 0.124 AC: 5564 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 7925 AN: 26120

East Asian (EAS) AF: 0.0169 AC: 671 AN: 39658

South Asian (SAS) AF: 0.262 AC: 22623 AN: 86200

European-Finnish (FIN) AF: 0.239 AC: 12707 AN: 53170

Middle Eastern (MID) AF: 0.262 AC: 1512 AN: 5762

European-Non Finnish (NFE) AF: 0.281 AC: 311871 AN: 1110048

Other (OTH) AF: 0.244 AC: 14689 AN: 60322

GnomAD4 genome AF: 0.193 AC: 29417 AN: 152110 Hom.: 3650 Cov.: 32 AF XY: 0.190 AC XY: 14149 AN XY: 74350

African (AFR) AF: 0.0505 AC: 2098 AN: 41520

American (AMR) AF: 0.174 AC: 2659 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1063 AN: 3470

East Asian (EAS) AF: 0.0257 AC: 133 AN: 5170

South Asian (SAS) AF: 0.254 AC: 1223 AN: 4822

European-Finnish (FIN) AF: 0.230 AC: 2435 AN: 10576

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.281 AC: 19073 AN: 67948

Other (OTH) AF: 0.217 AC: 457 AN: 2110

Alfa AF: 0.187 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

Submissions by phenotype

not provided Benign:3

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 02, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

CTU2-related disorder Benign:1

Nov 27, 2023

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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
PhyloP100		-0.56
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11641194; hg19: chr16-88773528; COSMIC: COSV107344099; COSMIC: COSV107344099;