Genetic Variant NM_006773.4:c.651-141A>G (chr2-117821509-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_006773.4(DDX18):c.651-141A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0827 in 1,084,898 control chromosomes in the GnomAD database, including 4,071 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: 𝑓 0.088 ( 629 hom., cov: 32)

Exomes 𝑓: 0.082 ( 3442 hom. )

Consequence

DDX18
NM_006773.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.57

Publications

6 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:

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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=-0.94).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

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.651-141A>G		intron	N/A	NP_006764.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DDX18	ENST00000263239.7	TSL:1 MANE Select	c.651-141A>G	intron	N/A	ENSP00000263239.2	Q9NVP1
DDX18	ENST00000898166.1		c.651-141A>G	intron	N/A	ENSP00000568225.1
DDX18	ENST00000921666.1		c.651-141A>G	intron	N/A	ENSP00000591725.1

Frequencies

GnomAD3 genomes

AF:

0.0876

AC:

13338

AN:

152192

Hom.:

620

Cov.:

show subpopulations

Gnomad AFR

AF:

0.119

Gnomad AMI

AF:

0.0658

Gnomad AMR

AF:

0.0564

Gnomad ASJ

AF:

0.0631

Gnomad EAS

AF:

0.000576

Gnomad SAS

AF:

0.0600

Gnomad FIN

AF:

0.0775

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0878

Gnomad OTH

AF:

0.0813

GnomAD4 exome

AF:

0.0819

AC:

76373

AN:

932588

Hom.:

3442

AF XY:

0.0815

AC XY:

38326

AN XY:

470176

show subpopulations

African (AFR)

AF:

0.126

AC:

2682

AN:

21332

American (AMR)

AF:

0.0461

AC:

1140

AN:

24750

Ashkenazi Jewish (ASJ)

AF:

0.0672

AC:

1204

AN:

17922

East Asian (EAS)

AF:

0.0000891

AC:

AN:

33660

South Asian (SAS)

AF:

0.0675

AC:

3994

AN:

59168

European-Finnish (FIN)

AF:

0.0822

AC:

3485

AN:

42404

Middle Eastern (MID)

AF:

0.0987

AC:

322

AN:

3262

European-Non Finnish (NFE)

AF:

0.0873

AC:

60088

AN:

688260

Other (OTH)

AF:

0.0826

AC:

3455

AN:

41830

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

3667

7335

11002

14670

18337

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1904

3808

5712

7616

9520

<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:

0.0878

AC:

13374

AN:

152310

Hom.:

629

Cov.:

AF XY:

0.0858

AC XY:

6389

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.119

AC:

4954

AN:

41572

American (AMR)

AF:

0.0562

AC:

860

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0631

AC:

219

AN:

3468

East Asian (EAS)

AF:

0.000578

AC:

AN:

5194

South Asian (SAS)

AF:

0.0601

AC:

290

AN:

4828

European-Finnish (FIN)

AF:

0.0775

AC:

822

AN:

10610

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0878

AC:

5976

AN:

68026

Other (OTH)

AF:

0.0804

AC:

170

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

634

1268

1902

2536

3170

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

296

444

592

740

<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:

0.0845

Hom.:

949

Bravo

AF:

0.0870

Asia WGS

AF:

0.0360

AC:

127

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.022

(source)

DANN

Benign

0.29

PhyloP100

-1.6

Mutation Taster

=100/0

polymorphism (auto)

(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

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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