16-88714227-GGTGT-GGTGTGTGT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 8P and 12B. PVS1 BP6_Very_Strong BS2

The NM_001012759.3(CTU2):c.1097+2_1097+5dup variant causes a frameshift, splice region change. Variant has been reported in ClinVar as Benign (★★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.46 (1367 hom., cov: 0)
  • Exomes 𝑓: 0.51 (14071 hom.)
  • Failed GnomAD Quality Control
• Consequence: CTU2 NM_001012759.3 frameshift, splice_region
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 5.54

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• BP6: Variant 16-88714227-G-GGTGT is Benign according to our data. Variant chr16-88714227-G-GGTGT is described in ClinVar as [Benign]. Clinvar id is 402575.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome at 1889 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTU2	NM_001012759.3	c.1097+2_1097+5dup		frameshift_variant, splice_region_variant		ENST00000453996.7
CTU2	NM_001012762.3	c.1097+2_1097+5dup		frameshift_variant, splice_region_variant
CTU2	NM_001318507.2	c.1310+2_1310+5dup		frameshift_variant, splice_region_variant
CTU2	NM_001318513.2	c.836+2_836+5dup		frameshift_variant, splice_region_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTU2	ENST00000453996.7	c.1097+2_1097+5dup		frameshift_variant, splice_region_variant		1	NM_001012759.3	P2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 19378 AN: 42188 Hom.: 1368 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.0385

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.400

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.457

GnomAD3 exomes AF: 0.104 AC: 25883 AN: 248558 Hom.: 1889 AF XY: 0.102 AC XY: 13743 AN XY: 134954

Gnomad AFR exome AF: 0.166

Gnomad AMR exome AF: 0.0416

Gnomad ASJ exome AF: 0.0905

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0297

Gnomad FIN exome AF: 0.148

Gnomad NFE exome AF: 0.145

Gnomad OTH exome AF: 0.110

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.507 AC: 190517 AN: 375902 Hom.: 14071 Cov.: 0 AF XY: 0.507 AC XY: 92586 AN XY: 182542

Gnomad4 AFR exome AF: 0.397

Gnomad4 AMR exome AF: 0.386

Gnomad4 ASJ exome AF: 0.445

Gnomad4 EAS exome AF: 0.0307

Gnomad4 SAS exome AF: 0.377

Gnomad4 FIN exome AF: 0.513

Gnomad4 NFE exome AF: 0.519

Gnomad4 OTH exome AF: 0.482

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.459 AC: 19380 AN: 42226 Hom.: 1367 Cov.: 0 AF XY: 0.455 AC XY: 9121 AN XY: 20030

Gnomad4 AFR AF: 0.404

Gnomad4 AMR AF: 0.373

Gnomad4 ASJ AF: 0.437

Gnomad4 EAS AF: 0.0385

Gnomad4 SAS AF: 0.333

Gnomad4 FIN AF: 0.495

Gnomad4 NFE AF: 0.517

Gnomad4 OTH AF: 0.452

EpiCase AF: 0.128

EpiControl AF: 0.119

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 24, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 27, 2021	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency (fails inbreeding coefficient filter) -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs149847195; hg19: chr16-88780635;