Genetic Variant DDX18:p.Cys183Tyr (chr2-117821194-G-A) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_006773.4(DDX18):c.548G>A(p.Cys183Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0114 in 1,606,406 control chromosomes in the GnomAD database, including 132 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0090 ( 9 hom., cov: 32)

Exomes 𝑓: 0.012 ( 123 hom. )

Consequence

DDX18
NM_006773.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.237

Publications

7 publications found

Variant links:

Genes affected

DDX18 (HGNC:2741): (DEAD-box helicase 18) 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 spliceosome 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, and it is activated by Myc protein. [provided by RefSeq, Jul 2008]

DDX18 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0040858686).

BP6

Variant 2-117821194-G-A is Benign according to our data. Variant chr2-117821194-G-A is described in ClinVar as Benign. ClinVar VariationId is 786730.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 9 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006773.4. 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
	DDX18	NM_006773.4	MANE Select	c.548G>A	p.Cys183Tyr	missense	Exon 4 of 14	NP_006764.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DDX18	ENST00000263239.7	TSL:1 MANE Select	c.548G>A	p.Cys183Tyr	missense	Exon 4 of 14	ENSP00000263239.2	Q9NVP1
DDX18	ENST00000898166.1		c.548G>A	p.Cys183Tyr	missense	Exon 4 of 15	ENSP00000568225.1
DDX18	ENST00000921666.1		c.548G>A	p.Cys183Tyr	missense	Exon 4 of 14	ENSP00000591725.1

Frequencies

GnomAD3 genomes

AF:

0.00899

AC:

1368

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00290

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0106

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.00521

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.0136

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0128

Gnomad OTH

AF:

0.0105

GnomAD2 exomes

AF:

0.00939

AC:

2317

AN:

246698

AF XY:

0.00923

show subpopulations

Gnomad AFR exome

AF:

0.00286

Gnomad AMR exome

AF:

0.0116

Gnomad ASJ exome

AF:

0.00462

Gnomad EAS exome

AF:

0.00500

Gnomad FIN exome

AF:

0.0133

Gnomad NFE exome

AF:

0.0121

Gnomad OTH exome

AF:

0.0102

GnomAD4 exome

AF:

0.0116

AC:

16928

AN:

1454168

Hom.:

123

Cov.:

AF XY:

0.0113

AC XY:

8183

AN XY:

723166

show subpopulations

African (AFR)

AF:

0.00196

AC:

AN:

33246

American (AMR)

AF:

0.0116

AC:

506

AN:

43520

Ashkenazi Jewish (ASJ)

AF:

0.00432

AC:

112

AN:

25940

East Asian (EAS)

AF:

0.00539

AC:

213

AN:

39484

South Asian (SAS)

AF:

0.00165

AC:

139

AN:

84310

European-Finnish (FIN)

AF:

0.0126

AC:

673

AN:

53266

Middle Eastern (MID)

AF:

0.00236

AC:

AN:

5502

European-Non Finnish (NFE)

AF:

0.0132

AC:

14584

AN:

1108870

Other (OTH)

AF:

0.0104

AC:

623

AN:

60030

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

740

1479

2219

2958

3698

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

564

1128

1692

2256

2820

<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:

0.00896

AC:

1364

AN:

152238

Hom.:

Cov.:

AF XY:

0.00881

AC XY:

656

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.00289

AC:

120

AN:

41550

American (AMR)

AF:

0.0106

AC:

162

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00375

AC:

AN:

3470

East Asian (EAS)

AF:

0.00503

AC:

AN:

5174

South Asian (SAS)

AF:

0.00186

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0136

AC:

144

AN:

10588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0127

AC:

867

AN:

68010

Other (OTH)

AF:

0.0104

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

153

229

306

382

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0110

Hom.:

Bravo

AF:

0.00870

TwinsUK

AF:

0.0140

AC:

ALSPAC

AF:

0.0122

AC:

ESP6500AA

AF:

0.00250

AC:

ESP6500EA

AF:

0.0109

AC:

ExAC

AF:

0.00849

AC:

1031

Asia WGS

AF:

0.00549

AC:

AN:

3472

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.79

CADD

Benign

6.6

(source)

DANN

Benign

0.40

DEOGEN2

Benign

0.014

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.11

MetaRNN

Benign

0.0041

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.0

PhyloP100

0.24

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.68

REVEL

Benign

0.038

Sift

Benign

0.050

Sift4G

Uncertain

0.031

Polyphen

0.035

Vest4

0.29

MVP

0.068

MPC

0.26

ClinPred

0.0013

GERP RS

-0.45

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.034

gMVP

0.35

Mutation Taster

=89/11

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over