rs1539163

Positions:

• chr10-68979874-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX21	NM_004728.4	c.2037+898C>T		intron_variant		ENST00000354185.9	NP_004719.2
DDX21	NM_001256910.2	c.1833+898C>T		intron_variant			NP_001243839.1
DDX21	NM_001410932.1	c.1875+898C>T		intron_variant			NP_001397861.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX21	ENST00000354185.9	c.2037+898C>T		intron_variant		1	NM_004728.4	ENSP00000346120	P1

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

Gnomad4 AFR AF: 0.0395

Gnomad4 AMR AF: 0.0525

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.0395

Gnomad4 SAS AF: 0.0700

Gnomad4 FIN AF: 0.0802

Gnomad4 NFE AF: 0.0701

Gnomad4 OTH AF: 0.0667

Alfa AF: 0.0712 Hom.: 406

Bravo AF: 0.0586

Asia WGS AF: 0.0340 AC: 117 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.44
DANN	Benign	0.40

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

Other links and lift over

dbSNP: rs1539163; hg19: chr10-70739630;