rs197414

chr1-111766501-C-Achr1-111766501-C-Gchr1-111766501-C-T

Variant summary

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

The NM_007204.5(DDX20):c.2077C>A(p.Arg693Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 1,613,790 control chromosomes in the GnomAD database, including 17,321 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.19 (3765 hom., cov: 32)
  • Exomes 𝑓: 0.13 (13556 hom.)
• Consequence: DDX20 NM_007204.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02

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 (MetaRNN=0.0013278723).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDX20	NM_007204.5	c.2077C>A	p.Arg693Ser	missense_variant	11/11	ENST00000369702.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDX20	ENST00000369702.5	c.2077C>A	p.Arg693Ser	missense_variant	11/11	1	NM_007204.5	P2

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28798 AN: 151906 Hom.: 3760 Cov.: 32

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.0868

Gnomad EAS AF: 0.00232

Gnomad SAS AF: 0.0836

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.180

GnomAD3 exomes AF: 0.121 AC: 30365 AN: 251332 Hom.: 2589 AF XY: 0.118 AC XY: 16002 AN XY: 135866

Gnomad AFR exome AF: 0.383

Gnomad AMR exome AF: 0.0640

Gnomad ASJ exome AF: 0.0853

Gnomad EAS exome AF: 0.00169

Gnomad SAS exome AF: 0.0903

Gnomad FIN exome AF: 0.148

Gnomad NFE exome AF: 0.127

Gnomad OTH exome AF: 0.113

GnomAD4 exome AF: 0.126 AC: 184170 AN: 1461766 Hom.: 13556 Cov.: 34 AF XY: 0.125 AC XY: 90726 AN XY: 727184

Gnomad4 AFR exome AF: 0.392

Gnomad4 AMR exome AF: 0.0692

Gnomad4 ASJ exome AF: 0.0869

Gnomad4 EAS exome AF: 0.00101

Gnomad4 SAS exome AF: 0.0893

Gnomad4 FIN exome AF: 0.153

Gnomad4 NFE exome AF: 0.127

Gnomad4 OTH exome AF: 0.126

GnomAD4 genome AF: 0.190 AC: 28842 AN: 152024 Hom.: 3765 Cov.: 32 AF XY: 0.185 AC XY: 13716 AN XY: 74316

Gnomad4 AFR AF: 0.374

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.0868

Gnomad4 EAS AF: 0.00232

Gnomad4 SAS AF: 0.0839

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.179

Alfa AF: 0.130 Hom.: 3734

Bravo AF: 0.194

TwinsUK AF: 0.126 AC: 466

ALSPAC AF: 0.124 AC: 478

ESP6500AA AF: 0.369 AC: 1627

ESP6500EA AF: 0.128 AC: 1099

ExAC AF: 0.127 AC: 15462

EpiCase AF: 0.127

EpiControl AF: 0.120

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.73
Cadd	Benign	6.0
Dann	Benign	0.85
DEOGEN2	Benign	0.081	T;.
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.39	T;T
MetaRNN	Benign	0.0013	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;.
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.92	N;N
REVEL	Benign	0.084
Sift	Benign	0.41	T;T
Sift4G	Benign	0.66	T;T
Polyphen		0.0020	B;B
Vest4		0.050
MPC		0.091
ClinPred		0.0057	T
GERP RS		4.1
Varity_R		0.094
gMVP		0.091

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: rs197414; hg19: chr1-112309123; COSMIC: COSV63778077; COSMIC: COSV63778077;