Variant chr5-118988303-G-T 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.209C>A(p.Thr70Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DTWD2
NM_173666.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.663

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=0.073972344).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DTWD2	NM_173666.4 linkuse as main transcript	c.209C>A	p.Thr70Asn	missense_variant	1/6	ENST00000510708.6	NP_775937.1	Q8NBA8-1
DTWD2	XM_011543338.4 linkuse as main transcript	c.209C>A	p.Thr70Asn	missense_variant	1/7		XP_011541640.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DTWD2	ENST00000510708.6 linkuse as main transcript	c.209C>A	p.Thr70Asn	missense_variant	1/6	1	NM_173666.4	ENSP00000425048.1	Q8NBA8-1
DTWD2	ENST00000515439.7 linkuse as main transcript	c.209C>A	p.Thr70Asn	missense_variant	1/4	5		ENSP00000424221.2	D6RBD8
DTWD2	ENST00000506980.2 linkuse as main transcript	n.209C>A		non_coding_transcript_exon_variant	1/5	5		ENSP00000425016.1	D6REE2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1370946

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

675684

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jan 09, 2024

The c.209C>A (p.T70N) alteration is located in exon 1 (coding exon 1) of the DTWD2 gene. This alteration results from a C to A substitution at nucleotide position 209, causing the threonine (T) at amino acid position 70 to be replaced by an asparagine (N). 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

0.064

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.68

DEOGEN2

Benign

0.017

T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.0059

LIST_S2

Benign

0.28

T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.074

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

N;.

PrimateAI

Uncertain

0.62

PROVEAN

Benign

0.26

N;N

REVEL

Benign

0.10

Sift

Benign

0.49

T;D

Sift4G

Benign

0.49

T;T

Polyphen

0.0

B;.

Vest4

0.21

MutPred

0.26

Loss of phosphorylation at T70 (P = 0.0221);Loss of phosphorylation at T70 (P = 0.0221);

MVP

0.055

MPC

0.032

ClinPred

0.064

GERP RS

2.1

Varity_R

0.058

gMVP

0.18

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over