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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CTU2	NM_001012759.3 link	c.282+552C>A	intron_variant	Intron 4 of 14	ENST00000453996.7	NP_001012777.1	Q2VPK5-1
CTU2	NM_001318507.2 link	c.282+552C>A	intron_variant	Intron 4 of 14		NP_001305436.1	Q2VPK5H3BSW6
CTU2	NM_001012762.3 link	c.282+552C>A	intron_variant	Intron 4 of 13		NP_001012780.1	Q2VPK5-5
CTU2	NM_001318513.2 link	c.21+552C>A	intron_variant	Intron 3 of 13		NP_001305442.1	Q2VPK5-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTU2	ENST00000453996.7 link	c.282+552C>A		intron_variant	Intron 4 of 14	1	NM_001012759.3	ENSP00000388320.2		Q2VPK5-1

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over