rs4895183

chr5-118880623-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173666.4(DTWD2):c.598-32405G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 151,988 control chromosomes in the GnomAD database, including 11,902 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.34 (11902 hom., cov: 33)
• Consequence: DTWD2 NM_173666.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.967

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DTWD2	NM_173666.4	c.598-32405G>A		intron_variant		ENST00000510708.6
DTWD2	NM_001308081.2	c.400-32405G>A		intron_variant
DTWD2	XM_011543338.4	c.658-32405G>A		intron_variant
DTWD2	XM_011543340.3	c.460-32405G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DTWD2	ENST00000510708.6	c.598-32405G>A		intron_variant		1	NM_173666.4	P1
DTWD2	ENST00000304058.8	c.400-32405G>A		intron_variant		1
DTWD2	ENST00000515439.7	c.310-32405G>A		intron_variant		5
DTWD2	ENST00000506980.2	c.405-32405G>A		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51526 AN: 151870 Hom.: 11867 Cov.: 33

Gnomad AFR AF: 0.658

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.0843

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.300

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.340 AC: 51618 AN: 151988 Hom.: 11902 Cov.: 33 AF XY: 0.337 AC XY: 25002 AN XY: 74278

Gnomad4 AFR AF: 0.658

Gnomad4 AMR AF: 0.280

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.0847

Gnomad4 SAS AF: 0.252

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.299

Alfa AF: 0.228 Hom.: 6771

Bravo AF: 0.362

Asia WGS AF: 0.196 AC: 681 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.23
Dann	Benign	0.41

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

Other links and lift over

dbSNP: rs4895183; hg19: chr5-118216318;