10-68967025-C-T

Variant names:

• chr10-68967025-C-T
• rs374055695
• NM_004728.4:c.912C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_004728.4(DDX21):​c.912C>T​(p.Arg304Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000734 in 1,607,356 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000075 (0 hom.)
• Consequence: DDX21 NM_004728.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.22
• Publications: 1 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 10-68967025-C-T is Benign according to our data. Variant chr10-68967025-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2640540.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.22 with no splicing effect.
• BS2: High AC in GnomAd4 at 9 AD gene.

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.912C>T	p.Arg304Arg	synonymous	Exon 6 of 15	NP_004719.2	Q9NR30-1
	DDX21	NM_001410932.1		c.912C>T	p.Arg304Arg	synonymous	Exon 6 of 14	NP_001397861.1	A0A8I5KYZ4
	DDX21	NM_001256910.2		c.708C>T	p.Arg236Arg	synonymous	Exon 6 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.912C>T	p.Arg304Arg	synonymous	Exon 6 of 15	ENSP00000346120.4	Q9NR30-1
	DDX21	ENST00000620315.2	TSL:1	c.708C>T	p.Arg236Arg	synonymous	Exon 6 of 15	ENSP00000480334.1	Q9NR30-2
	DDX21	ENST00000684824.1		c.912C>T	p.Arg304Arg	synonymous	Exon 6 of 16	ENSP00000508611.1	A0A8I5KNN2

Frequencies

GnomAD3 genomes AF: 0.0000595 AC: 9 AN: 151286 Hom.: 0 Cov.: 31

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: 0.000416

Gnomad FIN AF: 0.000192

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000736

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000120 AC: 30 AN: 249064 AF XY: 0.000178

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 FIN exome AF: 0.0000925

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000749 AC: 109 AN: 1455952 Hom.: 0 Cov.: 30 AF XY: 0.0000994 AC XY: 72 AN XY: 724126

African (AFR) AF: 0.00 AC: 0 AN: 33310

American (AMR) AF: 0.0000226 AC: 1 AN: 44222

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25934

East Asian (EAS) AF: 0.00 AC: 0 AN: 39578

South Asian (SAS) AF: 0.000469 AC: 40 AN: 85306

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53340

Middle Eastern (MID) AF: 0.000523 AC: 3 AN: 5738

European-Non Finnish (NFE) AF: 0.0000541 AC: 60 AN: 1108422

Other (OTH) AF: 0.0000832 AC: 5 AN: 60102

GnomAD4 genome AF: 0.0000594 AC: 9 AN: 151404 Hom.: 0 Cov.: 31 AF XY: 0.0000947 AC XY: 7 AN XY: 73890

African (AFR) AF: 0.00 AC: 0 AN: 41184

American (AMR) AF: 0.00 AC: 0 AN: 15116

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000417 AC: 2 AN: 4798

European-Finnish (FIN) AF: 0.000192 AC: 2 AN: 10432

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000736 AC: 5 AN: 67928

Other (OTH) AF: 0.00 AC: 0 AN: 2102

Alfa AF: 0.0000947 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	7.2
DANN	Benign	0.80
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs374055695; hg19: chr10-70726781;