5-118904812-A-T

Variant names:

• chr5-118904812-A-T
• rs17144806
• NM_173666.4:c.597+23725T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173666.4(DTWD2):​c.597+23725T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 151,976 control chromosomes in the GnomAD database, including 10,936 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 0.33 (10936 hom., cov: 32)
• Consequence: DTWD2 NM_173666.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0590
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DTWD2	NM_173666.4	c.597+23725T>A		intron_variant	Intron 4 of 5	ENST00000510708.6	NP_775937.1
DTWD2	NM_001308081.2	c.399+23725T>A		intron_variant	Intron 4 of 5		NP_001295010.1
DTWD2	XM_011543338.4	c.657+22167T>A		intron_variant	Intron 5 of 6		XP_011541640.3
DTWD2	XM_011543340.3	c.459+22167T>A		intron_variant	Intron 5 of 6		XP_011541642.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DTWD2	ENST00000510708.6	c.597+23725T>A		intron_variant	Intron 4 of 5	1	NM_173666.4	ENSP00000425048.1
DTWD2	ENST00000304058.8	c.399+23725T>A		intron_variant	Intron 4 of 5	1		ENSP00000302892.4
DTWD2	ENST00000515439.7	c.309+39747T>A		intron_variant	Intron 2 of 3	5		ENSP00000424221.2
DTWD2	ENST00000506980.2	n.404+34384T>A		intron_variant	Intron 3 of 4	5		ENSP00000425016.1

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49532 AN: 151858 Hom.: 10901 Cov.: 32

Gnomad AFR AF: 0.630

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.0835

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.290

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

GnomAD4 genome AF: 0.327 AC: 49625 AN: 151976 Hom.: 10936 Cov.: 32 AF XY: 0.322 AC XY: 23959 AN XY: 74298

African (AFR) AF: 0.630 AC: 26117 AN: 41436

American (AMR) AF: 0.221 AC: 3376 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 751 AN: 3466

East Asian (EAS) AF: 0.0840 AC: 436 AN: 5188

South Asian (SAS) AF: 0.255 AC: 1226 AN: 4816

European-Finnish (FIN) AF: 0.207 AC: 2189 AN: 10582

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.213 AC: 14435 AN: 67914

Other (OTH) AF: 0.290 AC: 611 AN: 2110

Alfa AF: 0.145 Hom.: 274

Bravo AF: 0.343

Asia WGS AF: 0.196 AC: 683 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.8
DANN	Benign	0.80
PhyloP100		-0.059
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17144806; hg19: chr5-118240507;