Variant 1-111766501-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_007204.5(DDX20):c.2077C>A(p.Arg693Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 1,613,790 control chromosomes in the GnomAD database, including 17,321 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.19 ( 3765 hom., cov: 32)

Exomes 𝑓: 0.13 ( 13556 hom. )

Consequence

DDX20
NM_007204.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.02

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013278723).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX20	NM_007204.5 link	c.2077C>A	p.Arg693Ser	missense_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.2077C>A	p.Arg693Ser	missense_variant	Exon 11 of 11	1	NM_007204.5	ENSP00000358716.4		Q9UHI6-1

Frequencies

GnomAD3 genomes

AF:

0.190

AC:

28798

AN:

151906

Hom.:

3760

Cov.:

show subpopulations

Gnomad AFR

AF:

0.374

Gnomad AMI

AF:

0.133

Gnomad AMR

AF:

0.115

Gnomad ASJ

AF:

0.0868

Gnomad EAS

AF:

0.00232

Gnomad SAS

AF:

0.0836

Gnomad FIN

AF:

0.148

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.129

Gnomad OTH

AF:

0.180

GnomAD3 exomes

AF:

0.121

AC:

30365

AN:

251332

Hom.:

2589

AF XY:

0.118

AC XY:

16002

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.383

Gnomad AMR exome

AF:

0.0640

Gnomad ASJ exome

AF:

0.0853

Gnomad EAS exome

AF:

0.00169

Gnomad SAS exome

AF:

0.0903

Gnomad FIN exome

AF:

0.148

Gnomad NFE exome

AF:

0.127

Gnomad OTH exome

AF:

0.113

GnomAD4 exome

AF:

0.126

AC:

184170

AN:

1461766

Hom.:

13556

Cov.:

AF XY:

0.125

AC XY:

90726

AN XY:

727184

show subpopulations

Gnomad4 AFR exome

AF:

0.392

Gnomad4 AMR exome

AF:

0.0692

Gnomad4 ASJ exome

AF:

0.0869

Gnomad4 EAS exome

AF:

0.00101

Gnomad4 SAS exome

AF:

0.0893

Gnomad4 FIN exome

AF:

0.153

Gnomad4 NFE exome

AF:

0.127

Gnomad4 OTH exome

AF:

0.126

GnomAD4 genome

AF:

0.190

AC:

28842

AN:

152024

Hom.:

3765

Cov.:

AF XY:

0.185

AC XY:

13716

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.374

Gnomad4 AMR

AF:

0.114

Gnomad4 ASJ

AF:

0.0868

Gnomad4 EAS

AF:

0.00232

Gnomad4 SAS

AF:

0.0839

Gnomad4 FIN

AF:

0.148

Gnomad4 NFE

AF:

0.129

Gnomad4 OTH

AF:

0.179

Alfa

AF:

0.130

Hom.:

3734

Bravo

AF:

0.194

TwinsUK

AF:

0.126

AC:

466

ALSPAC

AF:

0.124

AC:

478

ESP6500AA

AF:

0.369

AC:

1627

ESP6500EA

AF:

0.128

AC:

1099

ExAC

AF:

0.127

AC:

15462

EpiCase

AF:

0.127

EpiControl

AF:

0.120

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.73

CADD

Benign

6.0

DANN

Benign

0.85

DEOGEN2

Benign

0.081

T;.

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.39

T;T

MetaRNN

Benign

0.0013

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;.

PrimateAI

Benign

0.19

PROVEAN

Benign

-0.92

N;N

REVEL

Benign

0.084

Sift

Benign

0.41

T;T

Sift4G

Benign

0.66

T;T

Polyphen

0.0020

B;B

Vest4

0.050

MPC

0.091

ClinPred

0.0057

GERP RS

4.1

Varity_R

0.094

gMVP

0.091

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over