Genetic Variant DDX21:p.Ala187Asp (chr10-68962110-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004728.4(DDX21):c.560C>A(p.Ala187Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A187T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

DDX21
NM_004728.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.85

Publications

1 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16431466).

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.560C>A	p.Ala187Asp	missense	Exon 3 of 15	NP_004719.2	Q9NR30-1
DDX21	NM_001410932.1		c.560C>A	p.Ala187Asp	missense	Exon 3 of 14	NP_001397861.1	A0A8I5KYZ4
DDX21	NM_001256910.2		c.356C>A	p.Ala119Asp	missense	Exon 3 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.560C>A	p.Ala187Asp	missense	Exon 3 of 15	ENSP00000346120.4	Q9NR30-1
DDX21	ENST00000620315.2	TSL:1	c.356C>A	p.Ala119Asp	missense	Exon 3 of 15	ENSP00000480334.1	Q9NR30-2
DDX21	ENST00000684824.1		c.560C>A	p.Ala187Asp	missense	Exon 3 of 16	ENSP00000508611.1	A0A8I5KNN2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.19

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.22

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.78

M_CAP

Benign

0.025

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

PhyloP100

3.9

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-2.3

REVEL

Benign

0.069

Sift

Benign

0.63

Sift4G

Benign

0.65

Polyphen

0.036

Vest4

0.46

MutPred

0.17

Loss of glycosylation at S189 (P = 0.1224)

MVP

0.24

MPC

0.12

ClinPred

0.59

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.12

gMVP

0.60

Mutation Taster

=54/46

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over