rs197413

chr1-111766350-G-Achr1-111766350-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_007204.5(DDX20):c.1926G>A(p.Val642=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 1,613,552 control chromosomes in the GnomAD database, including 140,356 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 0.48 (19098 hom., cov: 32)
  • Exomes 𝑓: 0.40 (121258 hom.)
• Consequence: DDX20 NM_007204.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP7: Synonymous conserved (PhyloP=-1.14 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDX20	NM_007204.5	c.1926G>A	p.Val642=	synonymous_variant	11/11	ENST00000369702.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDX20	ENST00000369702.5	c.1926G>A	p.Val642=	synonymous_variant	11/11	1	NM_007204.5	P2

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73388 AN: 151986 Hom.: 19056 Cov.: 32

Gnomad AFR AF: 0.691

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.476

GnomAD3 exomes AF: 0.427 AC: 107035 AN: 250932 Hom.: 23926 AF XY: 0.413 AC XY: 56094 AN XY: 135658

Gnomad AFR exome AF: 0.699

Gnomad AMR exome AF: 0.531

Gnomad ASJ exome AF: 0.357

Gnomad EAS exome AF: 0.345

Gnomad SAS exome AF: 0.338

Gnomad FIN exome AF: 0.451

Gnomad NFE exome AF: 0.395

Gnomad OTH exome AF: 0.411

GnomAD4 exome AF: 0.402 AC: 587501 AN: 1461446 Hom.: 121258 Cov.: 49 AF XY: 0.399 AC XY: 289990 AN XY: 727038

Gnomad4 AFR exome AF: 0.710

Gnomad4 AMR exome AF: 0.524

Gnomad4 ASJ exome AF: 0.356

Gnomad4 EAS exome AF: 0.356

Gnomad4 SAS exome AF: 0.337

Gnomad4 FIN exome AF: 0.462

Gnomad4 NFE exome AF: 0.393

Gnomad4 OTH exome AF: 0.404

GnomAD4 genome AF: 0.483 AC: 73498 AN: 152106 Hom.: 19098 Cov.: 32 AF XY: 0.480 AC XY: 35657 AN XY: 74336

Gnomad4 AFR AF: 0.692

Gnomad4 AMR AF: 0.463

Gnomad4 ASJ AF: 0.350

Gnomad4 EAS AF: 0.348

Gnomad4 SAS AF: 0.326

Gnomad4 FIN AF: 0.447

Gnomad4 NFE AF: 0.398

Gnomad4 OTH AF: 0.474

Alfa AF: 0.400 Hom.: 21666

Bravo AF: 0.496

Asia WGS AF: 0.349 AC: 1221 AN: 3478

EpiCase AF: 0.394

EpiControl AF: 0.384

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.12
Dann	Benign	0.52

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: rs197413; hg19: chr1-112308972; COSMIC: COSV63778073; COSMIC: COSV63778073;