Variant 5-118928614-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_173666.4(DTWD2):c.520A>G(p.Ile174Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000114 in 1,602,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000099 ( 0 hom. )

Consequence

DTWD2
NM_173666.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.79

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 made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DTWD2	NM_173666.4 linkuse as main transcript	c.520A>G	p.Ile174Val	missense_variant	4/6	ENST00000510708.6	NP_775937.1	Q8NBA8-1
DTWD2	NM_001308081.2 linkuse as main transcript	c.322A>G	p.Ile108Val	missense_variant	4/6		NP_001295010.1	Q8NBA8-2
DTWD2	XM_011543338.4 linkuse as main transcript	c.520A>G	p.Ile174Val	missense_variant	4/7		XP_011541640.3
DTWD2	XM_011543340.3 linkuse as main transcript	c.322A>G	p.Ile108Val	missense_variant	4/7		XP_011541642.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DTWD2	ENST00000510708.6 linkuse as main transcript	c.520A>G	p.Ile174Val	missense_variant	4/6	1	NM_173666.4	ENSP00000425048.1	Q8NBA8-1
DTWD2	ENST00000304058.8 linkuse as main transcript	c.322A>G	p.Ile108Val	missense_variant	4/6	1		ENSP00000302892.4	Q8NBA8-2
DTWD2	ENST00000515439.7 linkuse as main transcript	c.309+15945A>G		intron_variant		5		ENSP00000424221.2	D6RBD8
DTWD2	ENST00000506980.2 linkuse as main transcript	n.404+10582A>G		intron_variant		5		ENSP00000425016.1	D6REE2

Frequencies

GnomAD3 genomes

AF:

0.000256

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000326

AC:

AN:

248364

Hom.:

AF XY:

0.000283

AC XY:

AN XY:

134420

show subpopulations

Gnomad AFR exome

AF:

0.000565

Gnomad AMR exome

AF:

0.000887

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00144

Gnomad SAS exome

AF:

0.000200

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000798

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.0000993

AC:

144

AN:

1449792

Hom.:

Cov.:

AF XY:

0.0000860

AC XY:

AN XY:

720714

show subpopulations

Gnomad4 AFR exome

AF:

0.000541

Gnomad4 AMR exome

AF:

0.000678

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000866

Gnomad4 SAS exome

AF:

0.000132

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.0000362

Gnomad4 OTH exome

AF:

0.000167

GnomAD4 genome

AF:

0.000250

AC:

AN:

152258

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00173

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000109

Hom.:

Bravo

AF:

0.000314

ExAC

AF:

0.000264

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3472

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2021

The c.520A>G (p.I174V) alteration is located in exon 4 (coding exon 4) of the DTWD2 gene. This alteration results from a A to G substitution at nucleotide position 520, causing the isoleucine (I) at amino acid position 174 to be replaced by a valine (V). 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

0.074

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.024

T;T

Eigen

Benign

-0.25

Eigen_PC

Benign

0.017

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.72

T;T

M_CAP

Benign

0.0049

MetaRNN

Benign

0.021

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.23

.;N

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.66

N;N

REVEL

Benign

0.040

Sift

Benign

0.17

T;T

Sift4G

Benign

0.68

T;T

Polyphen

0.0

.;B

Vest4

0.20

MVP

0.31

MPC

0.031

ClinPred

0.021

GERP RS

6.0

Varity_R

0.046

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.48

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.48

Position offset: -1

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over