10-68963462-C-T

Variant names:

• chr10-68963462-C-T
• NM_004728.4:c.779C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004728.4(DDX21):​c.779C>T​(p.Ala260Val) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: DDX21 NM_004728.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.75
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27423596).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX21	NM_004728.4	MANE Select	c.779C>T	p.Ala260Val	missense	Exon 4 of 15	NP_004719.2	Q9NR30-1
	DDX21	NM_001410932.1		c.779C>T	p.Ala260Val	missense	Exon 4 of 14	NP_001397861.1	A0A8I5KYZ4
	DDX21	NM_001256910.2		c.575C>T	p.Ala192Val	missense	Exon 4 of 15	NP_001243839.1	Q9NR30-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX21	ENST00000354185.9	TSL:1 MANE Select	c.779C>T	p.Ala260Val	missense	Exon 4 of 15	ENSP00000346120.4	Q9NR30-1
	DDX21	ENST00000620315.2	TSL:1	c.575C>T	p.Ala192Val	missense	Exon 4 of 15	ENSP00000480334.1	Q9NR30-2
	DDX21	ENST00000684824.1		c.779C>T	p.Ala260Val	missense	Exon 4 of 16	ENSP00000508611.1	A0A8I5KNN2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000137 AC: 2 AN: 1457976 Hom.: 1 Cov.: 30 AF XY: 0.00000276 AC XY: 2 AN XY: 725412

African (AFR) AF: 0.00 AC: 0 AN: 33302

American (AMR) AF: 0.00 AC: 0 AN: 43898

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25830

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.00 AC: 0 AN: 85740

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53300

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110228

Other (OTH) AF: 0.0000332 AC: 2 AN: 60256

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.3	L
PhyloP100		4.8
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.16
Sift	Benign	0.10	T
Sift4G	Benign	0.18	T
Polyphen		0.030	B
Vest4		0.21
MutPred		0.60		Gain of methylation at K256 (P = 0.0906)
MVP		0.42
MPC		0.73
ClinPred		0.56	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.11
gMVP		0.46
Mutation Taster		=75/25	polymorphism

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

Other links and lift over

hg19: chr10-70723218;