Variant 2-117821194-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 14/20 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

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:

DDX18 (HGNC:):

DDX18 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 786730.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX18	NM_006773.4 linkuse as main transcript	c.548G>A	p.Cys183Tyr	missense_variant	4/14	ENST00000263239.7	NP_006764.3	Q9NVP1Q8N254

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX18	ENST00000263239.7 linkuse as main transcript	c.548G>A	p.Cys183Tyr	missense_variant	4/14	1	NM_006773.4	ENSP00000263239.2		Q9NVP1
DDX18	ENST00000474694.1 linkuse as main transcript	n.534G>A		non_coding_transcript_exon_variant	5/9	5

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

GnomAD3 exomes

AF:

0.00939

AC:

2317

AN:

246698

Hom.:

AF XY:

0.00923

AC XY:

1231

AN XY:

133410

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 SAS exome

AF:

0.00159

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

Gnomad4 AFR exome

AF:

0.00196

Gnomad4 AMR exome

AF:

0.0116

Gnomad4 ASJ exome

AF:

0.00432

Gnomad4 EAS exome

AF:

0.00539

Gnomad4 SAS exome

AF:

0.00165

Gnomad4 FIN exome

AF:

0.0126

Gnomad4 NFE exome

AF:

0.0132

Gnomad4 OTH exome

AF:

0.0104

GnomAD4 genome

AF:

0.00896

AC:

1364

AN:

152238

Hom.:

Cov.:

AF XY:

0.00881

AC XY:

656

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.00289

Gnomad4 AMR

AF:

0.0106

Gnomad4 ASJ

AF:

0.00375

Gnomad4 EAS

AF:

0.00503

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.0136

Gnomad4 NFE

AF:

0.0127

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.0113

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

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 02, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.79

CADD

Benign

6.6

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

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over