22-38493652-C-T

Variant names:

• chr22-38493652-C-T
• rs2267390
• NM_006386.5:c.1387+58G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006386.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX17	NM_006386.5	MANE Select	c.1387+58G>A		intron	N/A	NP_006377.2
	DDX17	NM_001098504.2		c.1387+58G>A		intron	N/A	NP_001091974.1	A0A5H1ZRQ2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX17	ENST00000403230.3	TSL:1 MANE Select	c.1387+58G>A		intron	N/A	ENSP00000385536.2	Q92841-4
	DDX17	ENST00000396821.8	TSL:1	c.1387+58G>A		intron	N/A	ENSP00000380033.4	A0A5H1ZRQ2
	DDX17	ENST00000216019.11	TSL:1	n.1444+58G>A		intron	N/A

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

African (AFR) AF: 0.184 AC: 5165 AN: 28070

American (AMR) AF: 0.213 AC: 9099 AN: 42766

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 7175 AN: 24398

East Asian (EAS) AF: 0.375 AC: 14429 AN: 38440

South Asian (SAS) AF: 0.271 AC: 21698 AN: 79954

European-Finnish (FIN) AF: 0.351 AC: 18643 AN: 53154

Middle Eastern (MID) AF: 0.288 AC: 1529 AN: 5312

European-Non Finnish (NFE) AF: 0.297 AC: 262423 AN: 882960

Other (OTH) AF: 0.285 AC: 14889 AN: 52176

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

African (AFR) AF: 0.182 AC: 7531 AN: 41474

American (AMR) AF: 0.227 AC: 3474 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 1027 AN: 3470

East Asian (EAS) AF: 0.362 AC: 1870 AN: 5172

South Asian (SAS) AF: 0.282 AC: 1356 AN: 4810

European-Finnish (FIN) AF: 0.347 AC: 3664 AN: 10544

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.309 AC: 20985 AN: 67952

Other (OTH) AF: 0.272 AC: 576 AN: 2114

Alfa AF: 0.287 Hom.: 3033

Bravo AF: 0.254

Asia WGS AF: 0.305 AC: 1063 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.2
DANN	Benign	0.31
PhyloP100		-0.071
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2267390;

hg19: chr22-38889657;