dbSNP rs8052560: CTU2:c.282+552C>A (chr16-88710834-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001012759.3(CTU2):c.282+552C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.787 in 156,236 control chromosomes in the GnomAD database, including 48,539 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.79 ( 47371 hom., cov: 32)

Exomes 𝑓: 0.74 ( 1168 hom. )

Consequence

CTU2
NM_001012759.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.151

Publications

38 publications found

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 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)

CTU2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.902 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012759.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CTU2	NM_001012759.3	MANE Select	c.282+552C>A	intron	N/A	NP_001012777.1	Q2VPK5-1
CTU2	NM_001318507.2		c.282+552C>A	intron	N/A	NP_001305436.1	H3BSW6
CTU2	NM_001012762.3		c.282+552C>A	intron	N/A	NP_001012780.1	Q2VPK5-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CTU2	ENST00000453996.7	TSL:1 MANE Select	c.282+552C>A	intron	N/A	ENSP00000388320.2	Q2VPK5-1
CTU2	ENST00000567949.5	TSL:1	c.282+552C>A	intron	N/A	ENSP00000456908.1	H3BSW6
CTU2	ENST00000564105.5	TSL:1	n.203+552C>A	intron	N/A	ENSP00000454923.1	H3BNM3

Frequencies

GnomAD3 genomes

AF:

0.788

AC:

119701

AN:

151930

Hom.:

47344

Cov.:

show subpopulations

Gnomad AFR

AF:

0.765

Gnomad AMI

AF:

0.855

Gnomad AMR

AF:

0.837

Gnomad ASJ

AF:

0.891

Gnomad EAS

AF:

0.924

Gnomad SAS

AF:

0.825

Gnomad FIN

AF:

0.732

Gnomad MID

AF:

0.880

Gnomad NFE

AF:

0.779

Gnomad OTH

AF:

0.820

GnomAD4 exome

AF:

0.740

AC:

3099

AN:

4188

Hom.:

1168

Cov.:

AF XY:

0.746

AC XY:

1775

AN XY:

2380

show subpopulations

African (AFR)

AF:

0.729

AC:

AN:

American (AMR)

AF:

0.799

AC:

131

AN:

164

Ashkenazi Jewish (ASJ)

AF:

0.880

AC:

AN:

East Asian (EAS)

AF:

0.944

AC:

AN:

South Asian (SAS)

AF:

0.774

AC:

523

AN:

676

European-Finnish (FIN)

AF:

0.678

AC:

179

AN:

264

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.725

AC:

1956

AN:

2698

Other (OTH)

AF:

0.773

AC:

187

AN:

242

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

122

163

204

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.788

AC:

119781

AN:

152048

Hom.:

47371

Cov.:

AF XY:

0.789

AC XY:

58675

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.765

AC:

31698

AN:

41446

American (AMR)

AF:

0.837

AC:

12773

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.891

AC:

3095

AN:

3472

East Asian (EAS)

AF:

0.924

AC:

4770

AN:

5164

South Asian (SAS)

AF:

0.824

AC:

3970

AN:

4818

European-Finnish (FIN)

AF:

0.732

AC:

7741

AN:

10576

Middle Eastern (MID)

AF:

0.881

AC:

259

AN:

294

European-Non Finnish (NFE)

AF:

0.779

AC:

52964

AN:

67994

Other (OTH)

AF:

0.820

AC:

1731

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

1284

2568

3853

5137

6421

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

868

1736

2604

3472

4340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.782

Hom.:

84075

Bravo

AF:

0.794

Asia WGS

AF:

0.848

AC:

2950

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.5

(source)

DANN

Benign

0.62

PhyloP100

-0.15

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over