Variant 10-68960005-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000354185.9(DDX21):c.287G>C(p.Arg96Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000623 in 1,605,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000065 ( 0 hom. )

Consequence

DDX21
ENST00000354185.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.42

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 made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09110367).

BS2

High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
DDX21	NM_004728.4 linkuse as main transcript	c.287G>C	p.Arg96Thr	missense_variant	2/15	ENST00000354185.9	NP_004719.2
DDX21	NM_001410932.1 linkuse as main transcript	c.287G>C	p.Arg96Thr	missense_variant	2/14		NP_001397861.1
DDX21	NM_001256910.2 linkuse as main transcript	c.83G>C	p.Arg28Thr	missense_variant	2/15		NP_001243839.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX21	ENST00000354185.9 linkuse as main transcript	c.287G>C	p.Arg96Thr	missense_variant	2/15	1	NM_004728.4	ENSP00000346120	P1	Q9NR30-1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

151994

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000248

AC:

AN:

241650

Hom.:

AF XY:

0.0000230

AC XY:

AN XY:

130634

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:

0.0000541

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000654

AC:

AN:

1453028

Hom.:

Cov.:

AF XY:

0.0000540

AC XY:

AN XY:

722116

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.0000820

Gnomad4 OTH exome

AF:

0.0000666

GnomAD4 genome

AF:

0.0000329

AC:

AN:

151994

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74220

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000135

Hom.:

Bravo

AF:

0.0000529

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

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

Jun 13, 2024

The c.287G>C (p.R96T) alteration is located in exon 2 (coding exon 2) of the DDX21 gene. This alteration results from a G to C substitution at nucleotide position 287, causing the arginine (R) at amino acid position 96 to be replaced by a threonine (T). 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

0.12

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.14

T;.

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.43

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.71

T;T

M_CAP

Benign

0.0066

MetaRNN

Benign

0.091

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

N;.

MutationTaster

Benign

0.88

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.99

N;.

REVEL

Benign

0.070

Sift

Benign

0.048

D;.

Sift4G

Benign

0.43

T;T

Polyphen

0.0

B;.

Vest4

0.24

MVP

0.16

MPC

0.12

ClinPred

0.043

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.067

gMVP

0.068

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