chr22-38493652-C-T

Position:

• chr22-38493652-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.1387+58G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 1,359,242 control chromosomes in the GnomAD database, including 59,195 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 0.27 (5823 hom., cov: 32)
  • Exomes 𝑓: 0.29 (53372 hom.)
• Consequence: DDX17 NM_006386.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0710

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDX17	NM_006386.5	c.1387+58G>A		intron_variant		ENST00000403230.3
DDX17	NM_001098504.2	c.1387+58G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDX17	ENST00000403230.3	c.1387+58G>A		intron_variant		1	NM_006386.5	A2

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40911 AN: 151892 Hom.: 5817 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.403

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.268

GnomAD4 exome AF: 0.294 AC: 355050 AN: 1207230 Hom.: 53372 Cov.: 16 AF XY: 0.294 AC XY: 179962 AN XY: 612060

Gnomad4 AFR exome AF: 0.184

Gnomad4 AMR exome AF: 0.213

Gnomad4 ASJ exome AF: 0.294

Gnomad4 EAS exome AF: 0.375

Gnomad4 SAS exome AF: 0.271

Gnomad4 FIN exome AF: 0.351

Gnomad4 NFE exome AF: 0.297

Gnomad4 OTH exome AF: 0.285

GnomAD4 genome AF: 0.269 AC: 40944 AN: 152012 Hom.: 5823 Cov.: 32 AF XY: 0.271 AC XY: 20160 AN XY: 74312

Gnomad4 AFR AF: 0.182

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.296

Gnomad4 EAS AF: 0.362

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.347

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.272

Alfa AF: 0.279 Hom.: 1136

Bravo AF: 0.254

Asia WGS AF: 0.305 AC: 1063 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.2
DANN	Benign	0.31
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2267390; hg19: chr22-38889657;