Variant 5-118928716-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_173666.4(DTWD2):c.418T>G(p.Ser140Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,420,260 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

DTWD2
NM_173666.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.80

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07322183).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DTWD2	NM_173666.4 linkuse as main transcript	c.418T>G	p.Ser140Ala	missense_variant	4/6	ENST00000510708.6	NP_775937.1	Q8NBA8-1
DTWD2	NM_001308081.2 linkuse as main transcript	c.220T>G	p.Ser74Ala	missense_variant	4/6		NP_001295010.1	Q8NBA8-2
DTWD2	XM_011543338.4 linkuse as main transcript	c.418T>G	p.Ser140Ala	missense_variant	4/7		XP_011541640.3
DTWD2	XM_011543340.3 linkuse as main transcript	c.220T>G	p.Ser74Ala	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.418T>G	p.Ser140Ala	missense_variant	4/6	1	NM_173666.4	ENSP00000425048.1	Q8NBA8-1
DTWD2	ENST00000304058.8 linkuse as main transcript	c.220T>G	p.Ser74Ala	missense_variant	4/6	1		ENSP00000302892.4	Q8NBA8-2
DTWD2	ENST00000515439.7 linkuse as main transcript	c.309+15843T>G		intron_variant		5		ENSP00000424221.2	D6RBD8
DTWD2	ENST00000506980.2 linkuse as main transcript	n.404+10480T>G		intron_variant		5		ENSP00000425016.1	D6REE2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000437

AC:

AN:

228876

Hom.:

AF XY:

0.00

AC XY:

AN XY:

124182

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000347

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000141

AC:

AN:

1420260

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

704806

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000510

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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

Feb 06, 2023

The c.418T>G (p.S140A) alteration is located in exon 4 (coding exon 4) of the DTWD2 gene. This alteration results from a T to G substitution at nucleotide position 418, causing the serine (S) at amino acid position 140 to be replaced by an alanine (A). 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

0.056

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.0070

T;T

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.58

T;T

M_CAP

Benign

0.00094

MetaRNN

Benign

0.073

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.63

.;N

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.38

N;N

REVEL

Benign

0.057

Sift

Benign

0.88

T;T

Sift4G

Benign

0.67

T;T

Polyphen

0.0

.;B

Vest4

0.19

MutPred

0.45

.;Loss of disorder (P = 0.0417);

MVP

0.092

MPC

0.027

ClinPred

0.015

GERP RS

1.8

Varity_R

0.041

gMVP

0.33

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

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