10-68963354-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_004728.4(DDX21):c.671A>G(p.Lys224Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000587 in 1,614,176 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K224N) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0031 ( 3 hom., cov: 31)

Exomes 𝑓: 0.00032 ( 1 hom. )

Consequence

DDX21
NM_004728.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.11

Publications

4 publications found

Variant links:

Genes affected

DDX21 (HGNC:2744): (DExD-box helicase 21) 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 is an antigen recognized by autoimmune antibodies from a patient with watermelon stomach disease. This protein unwinds double-stranded RNA, folds single-stranded RNA, and may play important roles in ribosomal RNA biogenesis, RNA editing, RNA transport, and general transcription. [provided by RefSeq, Jul 2008]

DDX21 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01899311).

BP6

Variant 10-68963354-A-G is Benign according to our data. Variant chr10-68963354-A-G is described in ClinVar as Benign. ClinVar VariationId is 710606.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 474 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004728.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DDX21	NM_004728.4	MANE Select	c.671A>G	p.Lys224Arg	missense	Exon 4 of 15	NP_004719.2	Q9NR30-1
DDX21	NM_001410932.1		c.671A>G	p.Lys224Arg	missense	Exon 4 of 14	NP_001397861.1	A0A8I5KYZ4
DDX21	NM_001256910.2		c.467A>G	p.Lys156Arg	missense	Exon 4 of 15	NP_001243839.1	Q9NR30-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DDX21	ENST00000354185.9	TSL:1 MANE Select	c.671A>G	p.Lys224Arg	missense	Exon 4 of 15	ENSP00000346120.4	Q9NR30-1
DDX21	ENST00000620315.2	TSL:1	c.467A>G	p.Lys156Arg	missense	Exon 4 of 15	ENSP00000480334.1	Q9NR30-2
DDX21	ENST00000684824.1		c.671A>G	p.Lys224Arg	missense	Exon 4 of 16	ENSP00000508611.1	A0A8I5KNN2

Frequencies

GnomAD3 genomes

AF:

0.00311

AC:

474

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0107

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00150

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00334

GnomAD2 exomes

AF:

0.000903

AC:

227

AN:

251408

AF XY:

0.000603

show subpopulations

Gnomad AFR exome

AF:

0.0117

Gnomad AMR exome

AF:

0.000839

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000653

GnomAD4 exome

AF:

0.000324

AC:

474

AN:

1461838

Hom.:

Cov.:

AF XY:

0.000305

AC XY:

222

AN XY:

727222

show subpopulations

African (AFR)

AF:

0.0112

AC:

375

AN:

33472

American (AMR)

AF:

0.000939

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.000693

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000989

AC:

AN:

1111996

Other (OTH)

AF:

0.000679

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

122

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.00311

AC:

474

AN:

152338

Hom.:

Cov.:

AF XY:

0.00306

AC XY:

228

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.0107

AC:

443

AN:

41576

American (AMR)

AF:

0.00150

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68030

Other (OTH)

AF:

0.00331

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

100

125

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00116

Hom.:

Bravo

AF:

0.00359

ESP6500AA

AF:

0.00908

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00105

AC:

127

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.068

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.83

MetaRNN

Benign

0.019

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.12

PhyloP100

7.1

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.8

REVEL

Benign

0.061

Sift

Benign

0.11

Sift4G

Benign

0.13

Polyphen

0.0060

Vest4

0.31

MVP

0.52

MPC

0.072

ClinPred

0.052

GERP RS

4.2

Varity_R

0.28

gMVP

0.44

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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