Variant 5-118841026-C-A 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.788G>T(p.Arg263Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000658 in 152,056 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 0.0000066 ( 0 hom., cov: 33)

Consequence

DTWD2
NM_173666.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.45

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=0.18887049).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DTWD2	NM_173666.4 linkuse as main transcript	c.788G>T	p.Arg263Leu	missense_variant	6/6	ENST00000510708.6	NP_775937.1	Q8NBA8-1
DTWD2	NM_001308081.2 linkuse as main transcript	c.590G>T	p.Arg197Leu	missense_variant	6/6		NP_001295010.1	Q8NBA8-2
DTWD2	XM_011543338.4 linkuse as main transcript	c.848G>T	p.Arg283Leu	missense_variant	7/7		XP_011541640.3
DTWD2	XM_011543340.3 linkuse as main transcript	c.650G>T	p.Arg217Leu	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.788G>T	p.Arg263Leu	missense_variant	6/6	1	NM_173666.4	ENSP00000425048.1		Q8NBA8-1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152056

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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 22, 2023

The c.788G>T (p.R263L) alteration is located in exon 6 (coding exon 6) of the DTWD2 gene. This alteration results from a G to T substitution at nucleotide position 788, causing the arginine (R) at amino acid position 263 to be replaced by a leucine (L). 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

Uncertain

0.51

BayesDel_addAF

Benign

-0.012

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

T;T;T

Eigen

Benign

0.16

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.95

D;D;D

M_CAP

Benign

0.0061

MetaRNN

Benign

0.19

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

.;N;.

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-3.8

D;D;D

REVEL

Uncertain

0.35

Sift

Uncertain

0.0050

D;D;D

Sift4G

Uncertain

0.042

D;T;T

Polyphen

0.81

.;P;.

Vest4

0.25

MutPred

0.45

.;Gain of helix (P = 0.0199);.;

MVP

0.21

MPC

0.13

ClinPred

0.97

GERP RS

4.5

Varity_R

0.32

gMVP

0.36

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