10-68967024-G-A

Position:

chr10-68967024-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_004728.4(DDX21):c.911G>A(p.Arg304His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000685 in 1,605,366 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

DDX21
NM_004728.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.03

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.093081504).

BS2

High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX21	NM_004728.4 linkuse as main transcript	c.911G>A	p.Arg304His	missense_variant	6/15	ENST00000354185.9	NP_004719.2	Q9NR30-1
DDX21	NM_001410932.1 linkuse as main transcript	c.911G>A	p.Arg304His	missense_variant	6/14		NP_001397861.1
DDX21	NM_001256910.2 linkuse as main transcript	c.707G>A	p.Arg236His	missense_variant	6/15		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.911G>A	p.Arg304His	missense_variant	6/15	1	NM_004728.4	ENSP00000346120.4		Q9NR30-1

Frequencies

GnomAD3 genomes

AF:

0.00000661

AC:

AN:

151278

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000244

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000805

AC:

AN:

248576

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

134382

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000688

AC:

AN:

1454088

Hom.:

Cov.:

AF XY:

0.00000830

AC XY:

AN XY:

723140

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000723

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.00000661

AC:

AN:

151278

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73772

show subpopulations

Gnomad4 AFR

AF:

0.0000244

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 08, 2023

The c.911G>A (p.R304H) alteration is located in exon 6 (coding exon 6) of the DDX21 gene. This alteration results from a G to A substitution at nucleotide position 911, causing the arginine (R) at amino acid position 304 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.087

T;.

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.18

T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.093

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.3

L;.

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.51

N;.

REVEL

Benign

0.064

Sift

Benign

0.17

T;.

Sift4G

Benign

0.56

T;T

Polyphen

0.0020

B;.

Vest4

0.069

MutPred

0.56

Loss of methylation at R304 (P = 0.1385);.;

MVP

0.44

MPC

0.80

ClinPred

0.12

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.066

gMVP

0.26

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over