Genetic Variant DDX20:p.Val642Val (chr1-111766350-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_007204.5(DDX20):c.1926G>A(p.Val642Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 1,613,552 control chromosomes in the GnomAD database, including 140,356 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 0.48 ( 19098 hom., cov: 32)

Exomes 𝑓: 0.40 ( 121258 hom. )

Consequence

DDX20
NM_007204.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.15

Publications

21 publications found

Variant links:

Genes affected

DDX20 (HGNC:2743): (DEAD-box helicase 20) 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, which has an ATPase activity and is a component of the survival of motor neurons (SMN) complex. This protein interacts directly with SMN, the spinal muscular atrophy gene product, and may play a catalytic role in the function of the SMN complex on RNPs. [provided by RefSeq, Jul 2008]

DDX20 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP7

Synonymous conserved (PhyloP=-1.14 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX20	NM_007204.5 link	c.1926G>A	p.Val642Val	synonymous_variant	Exon 11 of 11	ENST00000369702.5	NP_009135.4	Q9UHI6-1Q9H4N4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX20	ENST00000369702.5 link	c.1926G>A	p.Val642Val	synonymous_variant	Exon 11 of 11	1	NM_007204.5	ENSP00000358716.4		Q9UHI6-1

Frequencies

GnomAD3 genomes

AF:

0.483

AC:

73388

AN:

151986

Hom.:

19056

Cov.:

show subpopulations

Gnomad AFR

AF:

0.691

Gnomad AMI

AF:

0.281

Gnomad AMR

AF:

0.462

Gnomad ASJ

AF:

0.350

Gnomad EAS

AF:

0.348

Gnomad SAS

AF:

0.326

Gnomad FIN

AF:

0.447

Gnomad MID

AF:

0.354

Gnomad NFE

AF:

0.398

Gnomad OTH

AF:

0.476

GnomAD2 exomes

AF:

0.427

AC:

107035

AN:

250932

AF XY:

0.413

show subpopulations

Gnomad AFR exome

AF:

0.699

Gnomad AMR exome

AF:

0.531

Gnomad ASJ exome

AF:

0.357

Gnomad EAS exome

AF:

0.345

Gnomad FIN exome

AF:

0.451

Gnomad NFE exome

AF:

0.395

Gnomad OTH exome

AF:

0.411

GnomAD4 exome

AF:

0.402

AC:

587501

AN:

1461446

Hom.:

121258

Cov.:

AF XY:

0.399

AC XY:

289990

AN XY:

727038

show subpopulations

African (AFR)

AF:

0.710

AC:

23755

AN:

33470

American (AMR)

AF:

0.524

AC:

23412

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.356

AC:

9303

AN:

26130

East Asian (EAS)

AF:

0.356

AC:

14150

AN:

39700

South Asian (SAS)

AF:

0.337

AC:

29102

AN:

86238

European-Finnish (FIN)

AF:

0.462

AC:

24645

AN:

53292

Middle Eastern (MID)

AF:

0.391

AC:

2255

AN:

5768

European-Non Finnish (NFE)

AF:

0.393

AC:

436496

AN:

1111756

Other (OTH)

AF:

0.404

AC:

24383

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

20084

40169

60253

80338

100422

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13660

27320

40980

54640

68300

<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:

0.483

AC:

73498

AN:

152106

Hom.:

19098

Cov.:

AF XY:

0.480

AC XY:

35657

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.692

AC:

28682

AN:

41472

American (AMR)

AF:

0.463

AC:

7077

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.350

AC:

1215

AN:

3468

East Asian (EAS)

AF:

0.348

AC:

1802

AN:

5172

South Asian (SAS)

AF:

0.326

AC:

1571

AN:

4824

European-Finnish (FIN)

AF:

0.447

AC:

4733

AN:

10588

Middle Eastern (MID)

AF:

0.361

AC:

106

AN:

294

European-Non Finnish (NFE)

AF:

0.398

AC:

27056

AN:

67976

Other (OTH)

AF:

0.474

AC:

1000

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1854

3707

5561

7414

9268

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

640

1280

1920

2560

3200

<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:

0.421

Hom.:

55127

Bravo

AF:

0.496

Asia WGS

AF:

0.349

AC:

1221

AN:

3478

EpiCase

AF:

0.394

EpiControl

AF:

0.384

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.12

(source)

DANN

Benign

0.52

PhyloP100

-1.1

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over