Genetic Variant DDX17:n.4790G>A (chr22-38488770-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000216019.11(DDX17):n.4790G>A variant causes a non coding transcript exon 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
ENST00000216019.11 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.122

Publications

14 publications found

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DDX17	NM_006386.5 link	c.1448-655G>A		intron_variant	Intron 11 of 12	ENST00000403230.3	NP_006377.2	Q92841-4
DDX17	NM_001098504.2 link	c.1448-655G>A		intron_variant	Intron 11 of 12		NP_001091974.1	A0A5H1ZRQ2Q59F66

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX17	ENST00000403230.3 link	c.1448-655G>A		intron_variant	Intron 11 of 12	1	NM_006386.5	ENSP00000385536.2		Q92841-4A0A1X7SBZ2

Frequencies

GnomAD3 genomes

AF:

0.0902

AC:

13727

AN:

152112

Hom.:

830

Cov.:

show subpopulations

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.:

AF XY:

0.113

AC XY:

43307

AN XY:

384770

show subpopulations

African (AFR)

AF:

0.0139

AC:

219

AN:

15790

American (AMR)

AF:

0.0656

AC:

AN:

1022

Ashkenazi Jewish (ASJ)

AF:

0.0938

AC:

483

AN:

5148

East Asian (EAS)

AF:

0.162

AC:

588

AN:

3634

South Asian (SAS)

AF:

0.126

AC:

2076

AN:

16470

European-Finnish (FIN)

AF:

0.175

AC:

AN:

274

Middle Eastern (MID)

AF:

0.119

AC:

193

AN:

1620

European-Non Finnish (NFE)

AF:

0.115

AC:

87519

AN:

761944

Other (OTH)

AF:

0.107

AC:

2918

AN:

27294

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

4072

8144

12217

16289

20361

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4368

8736

13104

17472

21840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0901

AC:

13720

AN:

152232

Hom.:

828

Cov.:

AF XY:

0.0926

AC XY:

6888

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.0209

AC:

870

AN:

41538

American (AMR)

AF:

0.0673

AC:

1029

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0901

AC:

313

AN:

3472

East Asian (EAS)

AF:

0.158

AC:

820

AN:

5188

South Asian (SAS)

AF:

0.125

AC:

603

AN:

4830

European-Finnish (FIN)

AF:

0.163

AC:

1722

AN:

10586

Middle Eastern (MID)

AF:

0.146

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.116

AC:

7916

AN:

68002

Other (OTH)

AF:

0.0903

AC:

191

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

625

1251

1876

2502

3127

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

162

324

486

648

810

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0775

Hom.:

221

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

(source)

DANN

Benign

0.68

PhyloP100

-0.12

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over