Variant 10-68963354-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

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

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:

DDX21 (HGNC:):

DDX21 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 710606.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 474 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX21	NM_004728.4 linkuse as main transcript	c.671A>G	p.Lys224Arg	missense_variant	4/15	ENST00000354185.9	NP_004719.2	Q9NR30-1
DDX21	NM_001410932.1 linkuse as main transcript	c.671A>G	p.Lys224Arg	missense_variant	4/14		NP_001397861.1
DDX21	NM_001256910.2 linkuse as main transcript	c.467A>G	p.Lys156Arg	missense_variant	4/15		NP_001243839.1	Q9NR30-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX21	ENST00000354185.9 linkuse as main transcript	c.671A>G	p.Lys224Arg	missense_variant	4/15	1	NM_004728.4	ENSP00000346120.4		Q9NR30-1

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

GnomAD3 exomes

AF:

0.000903

AC:

227

AN:

251408

Hom.:

AF XY:

0.000603

AC XY:

AN XY:

135876

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 SAS exome

AF:

0.00

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

Gnomad4 AFR exome

AF:

0.0112

Gnomad4 AMR exome

AF:

0.000939

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000989

Gnomad4 OTH exome

AF:

0.000679

GnomAD4 genome

AF:

0.00311

AC:

474

AN:

152338

Hom.:

Cov.:

AF XY:

0.00306

AC XY:

228

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.0107

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.000625

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

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 04, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

T;.

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.068

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.83

T;T

MetaRNN

Benign

0.019

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.12

N;.

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.8

N;.

REVEL

Benign

0.061

Sift

Benign

0.11

T;.

Sift4G

Benign

0.13

T;T

Polyphen

0.0060

B;.

Vest4

0.31

MVP

0.52

MPC

0.072

ClinPred

0.052

GERP RS

4.2

Varity_R

0.28

gMVP

0.44

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

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