Variant 5-118840942-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_173666.4(DTWD2):c.872T>G(p.Leu291Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,374 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: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

DTWD2
NM_173666.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.79

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33144823).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DTWD2	NM_173666.4 linkuse as main transcript	c.872T>G	p.Leu291Trp	missense_variant	6/6	ENST00000510708.6	NP_775937.1	Q8NBA8-1
DTWD2	NM_001308081.2 linkuse as main transcript	c.674T>G	p.Leu225Trp	missense_variant	6/6		NP_001295010.1	Q8NBA8-2
DTWD2	XM_011543338.4 linkuse as main transcript	c.932T>G	p.Leu311Trp	missense_variant	7/7		XP_011541640.3
DTWD2	XM_011543340.3 linkuse as main transcript	c.734T>G	p.Leu245Trp	missense_variant	7/7		XP_011541642.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DTWD2	ENST00000510708.6 linkuse as main transcript	c.872T>G	p.Leu291Trp	missense_variant	6/6	1	NM_173666.4	ENSP00000425048.1		Q8NBA8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

250958

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135672

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461374

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726970

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000630

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.00000756

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

Dec 13, 2021

The c.872T>G (p.L291W) alteration is located in exon 6 (coding exon 6) of the DTWD2 gene. This alteration results from a T to G substitution at nucleotide position 872, causing the leucine (L) at amino acid position 291 to be replaced by a tryptophan (W). 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

0.31

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Pathogenic

DANN

Benign

0.97

DEOGEN2

Benign

0.042

T;T;T

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.83

T;T;T

M_CAP

Benign

0.0097

MetaRNN

Benign

0.33

T;T;T

MetaSVM

Benign

-0.61

MutationAssessor

Benign

1.2

.;L;.

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-2.3

N;N;N

REVEL

Uncertain

0.29

Sift

Uncertain

0.021

D;D;D

Sift4G

Uncertain

0.021

D;D;D

Polyphen

1.0

.;D;.

Vest4

0.53

MutPred

0.25

.;Loss of stability (P = 0.1114);.;

MVP

0.47

MPC

0.27

ClinPred

0.81

GERP RS

5.4

Varity_R

0.16

gMVP

0.39

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