rs17144806

Positions:

• chr5-118904812-A-G
• chr5-118904812-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_173666.4(DTWD2):​c.597+23725T>C variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DTWD2 NM_173666.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0590

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DTWD2	NM_173666.4	c.597+23725T>C		intron_variant		ENST00000510708.6
DTWD2	NM_001308081.2	c.399+23725T>C		intron_variant
DTWD2	XM_011543338.4	c.657+22167T>C		intron_variant
DTWD2	XM_011543340.3	c.459+22167T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DTWD2	ENST00000510708.6	c.597+23725T>C		intron_variant		1	NM_173666.4	P1
DTWD2	ENST00000304058.8	c.399+23725T>C		intron_variant		1
DTWD2	ENST00000515439.7	c.309+39747T>C		intron_variant		5
DTWD2	ENST00000506980.2	c.404+34384T>C		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.7
DANN	Benign	0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17144806; hg19: chr5-118240507;