10-68979874-C-T

Variant names:

• chr10-68979874-C-T
• rs1539163
• NM_004728.4:c.2037+898C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004728.4(DDX21):​c.2037+898C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.061 in 152,240 control chromosomes in the GnomAD database, including 325 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.061 (325 hom., cov: 32)
• Consequence: DDX21 NM_004728.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0685 is higher than 0.05.

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.2037+898C>T		intron	N/A	NP_004719.2	Q9NR30-1
	DDX21	NM_001410932.1		c.1875+898C>T		intron	N/A	NP_001397861.1	A0A8I5KYZ4
	DDX21	NM_001256910.2		c.1833+898C>T		intron	N/A	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.2037+898C>T		intron	N/A	ENSP00000346120.4	Q9NR30-1
	DDX21	ENST00000620315.2	TSL:1	c.1833+898C>T		intron	N/A	ENSP00000480334.1	Q9NR30-2
	DDX21	ENST00000684824.1		c.2112+898C>T		intron	N/A	ENSP00000508611.1	A0A8I5KNN2

Frequencies

GnomAD3 genomes AF: 0.0610 AC: 9275 AN: 152122 Hom.: 323 Cov.: 32

Gnomad AFR AF: 0.0395

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.0525

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.0394

Gnomad SAS AF: 0.0697

Gnomad FIN AF: 0.0802

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0701

Gnomad OTH AF: 0.0674

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0610 AC: 9282 AN: 152240 Hom.: 325 Cov.: 32 AF XY: 0.0609 AC XY: 4532 AN XY: 74436

African (AFR) AF: 0.0395 AC: 1640 AN: 41556

American (AMR) AF: 0.0525 AC: 802 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 380 AN: 3468

East Asian (EAS) AF: 0.0395 AC: 205 AN: 5186

South Asian (SAS) AF: 0.0700 AC: 338 AN: 4832

European-Finnish (FIN) AF: 0.0802 AC: 850 AN: 10596

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0701 AC: 4770 AN: 68002

Other (OTH) AF: 0.0667 AC: 141 AN: 2114

Alfa AF: 0.0700 Hom.: 521

Bravo AF: 0.0586

Asia WGS AF: 0.0340 AC: 117 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.44
DANN	Benign	0.40
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs1539163; hg19: chr10-70739630;