Genetic Variant DTWD2:p.Asp53Gly (chr5-118988354-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_173666.4(DTWD2):c.158A>G(p.Asp53Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000305 in 1,562,512 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00031 ( 0 hom. )

Consequence

DTWD2
NM_173666.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.979

Publications

0 publications found

Variant links:

Genes affected

DTWD2 (HGNC:19334): (DTW domain containing 2) Enables tRNA-uridine aminocarboxypropyltransferase activity. Involved in tRNA modification. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

DTWD2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14894378).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DTWD2	NM_173666.4 link	c.158A>G	p.Asp53Gly	missense_variant	Exon 1 of 6	ENST00000510708.6	NP_775937.1	Q8NBA8-1
DTWD2	XM_011543338.4 link	c.158A>G	p.Asp53Gly	missense_variant	Exon 1 of 7		XP_011541640.3
DTWD2	NM_001308081.2 link	c.-205A>G		upstream_gene_variant			NP_001295010.1	Q8NBA8-2
DTWD2	XM_011543340.3 link	c.-205A>G		upstream_gene_variant			XP_011541642.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DTWD2	ENST00000510708.6 link	c.158A>G	p.Asp53Gly	missense_variant	Exon 1 of 6	1	NM_173666.4	ENSP00000425048.1	Q8NBA8-1
DTWD2	ENST00000515439.7 link	c.158A>G	p.Asp53Gly	missense_variant	Exon 1 of 4	5		ENSP00000424221.2	D6RBD8
DTWD2	ENST00000506980.2 link	n.158A>G		non_coding_transcript_exon_variant	Exon 1 of 5	5		ENSP00000425016.1	D6REE2
DTWD2	ENST00000304058.8 link	c.-205A>G		upstream_gene_variant		1		ENSP00000302892.4	Q8NBA8-2

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000573

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000250

AC:

AN:

160256

AF XY:

0.0000226

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000639

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000308

AC:

435

AN:

1410320

Hom.:

Cov.:

AF XY:

0.000261

AC XY:

182

AN XY:

697678

show subpopulations

African (AFR)

AF:

0.0000318

AC:

AN:

31402

American (AMR)

AF:

0.0000267

AC:

AN:

37490

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25156

East Asian (EAS)

AF:

0.00

AC:

AN:

36474

South Asian (SAS)

AF:

0.00

AC:

AN:

81020

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4254

European-Non Finnish (NFE)

AF:

0.000370

AC:

403

AN:

1088572

Other (OTH)

AF:

0.000514

AC:

AN:

58334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

107

142

178

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000276

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41452

American (AMR)

AF:

0.0000654

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000573

AC:

AN:

68020

Other (OTH)

AF:

0.000478

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.000521

Hom.:

Bravo

AF:

0.000208

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000274

AC:

ExAC

AF:

0.0000270

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 28, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.158A>G (p.D53G) alteration is located in exon 1 (coding exon 1) of the DTWD2 gene. This alteration results from a A to G substitution at nucleotide position 158, causing the aspartic acid (D) at amino acid position 53 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.057

T;T

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.54

T;T

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.97

L;.

PhyloP100

0.98

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-2.5

D;N

REVEL

Benign

0.15

Sift

Benign

0.15

T;D

Sift4G

Benign

0.20

T;T

Polyphen

0.0020

B;.

Vest4

0.32

MVP

0.30

MPC

0.035

ClinPred

0.10

GERP RS

4.2

PromoterAI

-0.12

Neutral

(source)

Varity_R

0.28

gMVP

0.30

Mutation Taster

=70/30

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over