16-88714227-GGTGT-GGTGTGTGT

Variant names:

• chr16-88714227-G-GGTGT
• rs149847195
• NM_001012759.3:c.1097+2_1097+5dupTGTG

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PVS1_Moderate BP6_Very_Strong

The ENST00000453996.7(CTU2):​c.1097_1097+1insGTGT variant causes a splice donor, intron change. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (1367 hom., cov: 0)
  • Exomes 𝑓: 0.51 (14071 hom.)
  • Failed GnomAD Quality Control
• Consequence: CTU2 ENST00000453996.7 splice_donor, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 5.54
• Publications: 4 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: Likely_benign. The variant received -6 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.059431523 fraction of the gene. Cryptic splice site detected, with MaxEntScore 7, offset of 0 (no position change), new splice context is: cagGTgtgt. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.
• BP6: Variant 16-88714227-G-GGTGT is Benign according to our data. Variant chr16-88714227-G-GGTGT is described in ClinVar as Benign. ClinVar VariationId is 402575.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000453996.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTU2	NM_001012759.3	MANE Select	c.1097+2_1097+5dupTGTG		splice_region intron	N/A	NP_001012777.1	Q2VPK5-1
	CTU2	NM_001318507.2		c.1310+2_1310+5dupTGTG		splice_region intron	N/A	NP_001305436.1	H3BSW6
	CTU2	NM_001012762.3		c.1097+2_1097+5dupTGTG		splice_region intron	N/A	NP_001012780.1	Q2VPK5-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTU2	ENST00000453996.7	TSL:1 MANE Select	c.1097_1097+1insGTGT		splice_donor intron	N/A	ENSP00000388320.2	Q2VPK5-1
	CTU2	ENST00000567949.5	TSL:1	c.1310_1310+1insGTGT		splice_donor intron	N/A	ENSP00000456908.1	H3BSW6
	CTU2	ENST00000564105.5	TSL:1	n.*808_*808+1insGTGT		splice_donor intron	N/A	ENSP00000454923.1	H3BNM3

Frequencies

GnomAD3 genomes AF: 0.459 AC: 19378 AN: 42188 Hom.: 1368 Cov.: 0

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

GnomAD2 exomes AF: 0.104 AC: 25883 AN: 248558 AF XY: 0.102

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 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

African (AFR) AF: 0.397 AC: 5404 AN: 13606

American (AMR) AF: 0.386 AC: 1977 AN: 5118

Ashkenazi Jewish (ASJ) AF: 0.445 AC: 2441 AN: 5488

East Asian (EAS) AF: 0.0307 AC: 7 AN: 228

South Asian (SAS) AF: 0.377 AC: 2590 AN: 6874

European-Finnish (FIN) AF: 0.513 AC: 7974 AN: 15550

Middle Eastern (MID) AF: 0.391 AC: 151 AN: 386

European-Non Finnish (NFE) AF: 0.519 AC: 163263 AN: 314728

Other (OTH) AF: 0.482 AC: 6710 AN: 13924

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

African (AFR) AF: 0.404 AC: 6796 AN: 16806

American (AMR) AF: 0.373 AC: 788 AN: 2112

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 331 AN: 758

East Asian (EAS) AF: 0.0385 AC: 2 AN: 52

South Asian (SAS) AF: 0.333 AC: 120 AN: 360

European-Finnish (FIN) AF: 0.495 AC: 1539 AN: 3106

Middle Eastern (MID) AF: 0.375 AC: 3 AN: 8

European-Non Finnish (NFE) AF: 0.517 AC: 9516 AN: 18414

Other (OTH) AF: 0.452 AC: 209 AN: 462

Alfa AF: 0.00 Hom.: 0

EpiCase AF: 0.128

EpiControl AF: 0.119

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.5
Mutation Taster		=54/46	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs149847195; hg19: chr16-88780635; COSMIC: COSV56332817; COSMIC: COSV56332817;