22-38488770-C-T

Position:

• chr22-38488770-C-T

Variant summary

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

The NM_006386.5(DDX17):​c.1448-655G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 985,428 control chromosomes in the GnomAD database, including 6,335 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 0.090 (828 hom., cov: 32)
  • Exomes 𝑓: 0.11 (5507 hom.)
• Consequence: DDX17 NM_006386.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.122

Genes affected

DDX17 (HGNC:2740): (DEAD-box helicase 17) DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure, such as translation initiation, nuclear and mitochondrial splicing, and ribosome and splicesosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box protein, which is an ATPase activated by a variety of RNA species, but not by dsDNA. This protein, and that encoded by DDX5 gene, are more closely related to each other than to any other member of the DEAD box family. This gene can encode multiple isoforms due to both alternative splicing and the use of alternative translation initiation codons, including a non-AUG (CUG) start codon. [provided by RefSeq, Apr 2011]

DDX17 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX17	NM_006386.5	c.1448-655G>A		intron_variant		ENST00000403230.3	NP_006377.2
DDX17	NM_001098504.2	c.1448-655G>A		intron_variant			NP_001091974.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX17	ENST00000403230.3	c.1448-655G>A		intron_variant		1	NM_006386.5	ENSP00000385536.2

Frequencies

GnomAD3 genomes AF: 0.0902 AC: 13727 AN: 152112 Hom.: 830 Cov.: 32

Gnomad AFR AF: 0.0210

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.0674

Gnomad ASJ AF: 0.0901

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.0913

GnomAD4 exome AF: 0.113 AC: 94111 AN: 833196 Hom.: 5507 Cov.: 30 AF XY: 0.113 AC XY: 43307 AN XY: 384770

Gnomad4 AFR exome AF: 0.0139

Gnomad4 AMR exome AF: 0.0656

Gnomad4 ASJ exome AF: 0.0938

Gnomad4 EAS exome AF: 0.162

Gnomad4 SAS exome AF: 0.126

Gnomad4 FIN exome AF: 0.175

Gnomad4 NFE exome AF: 0.115

Gnomad4 OTH exome AF: 0.107

GnomAD4 genome AF: 0.0901 AC: 13720 AN: 152232 Hom.: 828 Cov.: 32 AF XY: 0.0926 AC XY: 6888 AN XY: 74420

Gnomad4 AFR AF: 0.0209

Gnomad4 AMR AF: 0.0673

Gnomad4 ASJ AF: 0.0901

Gnomad4 EAS AF: 0.158

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.116

Gnomad4 OTH AF: 0.0903

Alfa AF: 0.0565 Hom.: 83

Bravo AF: 0.0822

Asia WGS AF: 0.127 AC: 444 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	14
DANN	Benign	0.68

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs5750609; hg19: chr22-38884775;