rs149847195

chr16-88714227-GGTGT-Gchr16-88714227-GGTGT-GGTGTGTGTchr16-88714227-GGTGT-GGTGTGTGTGGGTGTGTGTchr16-88714227-GGTGT-GGTGTGTGTGGGTGTGTGTGGGTGTGTGT

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PP3_Moderate

The NM_001012759.3(CTU2):c.1097+2_1097+5del variant causes a splice donor, splice donor region, intron change. 1/1 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 0)
• Consequence: CTU2 NM_001012759.3 splice_donor, splice_donor_region, intron
• Clinical Significance: Not reported in ClinVar
• 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 Pathogenic. Variant got 10 ACMG points.

• PVS1: Splicing variant, LoF is a know mechanism of disease, Cryptic splice site detected, with MaxEntScore 3.1, offset of 2, new splice context is: gggGTgtgt. Cryptic site results in frameshift change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.
• PP3: Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 0

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

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.95		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.63		Position offset: 6
DS_DL_spliceai		0.95		Position offset: 0

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;