rs17569368

chr1-111761169-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007204.5(DDX20):c.962+44A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0388 in 1,611,488 control chromosomes in the GnomAD database, including 1,458 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 0.036 (133 hom., cov: 33)
  • Exomes 𝑓: 0.039 (1325 hom.)
• Consequence: DDX20 NM_007204.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.525

Genes affected

DDX20 (HGNC:2743): (DEAD-box helicase 20) 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 has an ATPase activity and is a component of the survival of motor neurons (SMN) complex. This protein interacts directly with SMN, the spinal muscular atrophy gene product, and may play a catalytic role in the function of the SMN complex on RNPs. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDX20	NM_007204.5	c.962+44A>T		intron_variant		ENST00000369702.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDX20	ENST00000369702.5	c.962+44A>T		intron_variant		1	NM_007204.5	P2

Frequencies

GnomAD3 genomes AF: 0.0356 AC: 5414 AN: 152218 Hom.: 131 Cov.: 33

Gnomad AFR AF: 0.0212

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0595

Gnomad ASJ AF: 0.0438

Gnomad EAS AF: 0.0724

Gnomad SAS AF: 0.0300

Gnomad FIN AF: 0.0299

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0372

Gnomad OTH AF: 0.0392

GnomAD3 exomes AF: 0.0477 AC: 11908 AN: 249606 Hom.: 399 AF XY: 0.0448 AC XY: 6051 AN XY: 134952

Gnomad AFR exome AF: 0.0180

Gnomad AMR exome AF: 0.107

Gnomad ASJ exome AF: 0.0457

Gnomad EAS exome AF: 0.0743

Gnomad SAS exome AF: 0.0273

Gnomad FIN exome AF: 0.0332

Gnomad NFE exome AF: 0.0379

Gnomad OTH exome AF: 0.0532

GnomAD4 exome AF: 0.0391 AC: 57034 AN: 1459152 Hom.: 1325 Cov.: 32 AF XY: 0.0385 AC XY: 27965 AN XY: 725804

Gnomad4 AFR exome AF: 0.0190

Gnomad4 AMR exome AF: 0.101

Gnomad4 ASJ exome AF: 0.0479

Gnomad4 EAS exome AF: 0.0780

Gnomad4 SAS exome AF: 0.0279

Gnomad4 FIN exome AF: 0.0346

Gnomad4 NFE exome AF: 0.0365

Gnomad4 OTH exome AF: 0.0412

GnomAD4 genome AF: 0.0357 AC: 5431 AN: 152336 Hom.: 133 Cov.: 33 AF XY: 0.0350 AC XY: 2609 AN XY: 74488

Gnomad4 AFR AF: 0.0215

Gnomad4 AMR AF: 0.0596

Gnomad4 ASJ AF: 0.0438

Gnomad4 EAS AF: 0.0728

Gnomad4 SAS AF: 0.0306

Gnomad4 FIN AF: 0.0299

Gnomad4 NFE AF: 0.0372

Gnomad4 OTH AF: 0.0383

Alfa AF: 0.0380 Hom.: 24

Bravo AF: 0.0391

Asia WGS AF: 0.0510 AC: 179 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	17
Dann	Benign	0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs17569368; hg19: chr1-112303791; COSMIC: COSV63831602; COSMIC: COSV63831602;