rs197414

Variant names:

• chr1-111766501-C-A
• rs197414
• NM_007204.5:c.2077C>A
• DDX20 p.Arg693Ser

Your query was ambiguous. Multiple possible variants found:

• chr1-111766501-C-A
• chr1-111766501-C-G
• chr1-111766501-C-T

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 58 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007204.5. 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
	DDX20	NM_007204.5	MANE Select	c.2077C>A	p.Arg693Ser	missense	Exon 11 of 11	NP_009135.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX20	ENST00000369702.5	TSL:1 MANE Select	c.2077C>A	p.Arg693Ser	missense	Exon 11 of 11	ENSP00000358716.4	Q9UHI6-1
	DDX20	ENST00000937510.1		c.2173C>A	p.Arg725Ser	missense	Exon 12 of 12	ENSP00000607569.1
	DDX20	ENST00000679724.1		c.2077C>A	p.Arg693Ser	missense	Exon 12 of 12	ENSP00000505857.1	Q9UHI6-1

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

GnomAD2 exomes AF: 0.121 AC: 30365 AN: 251332 AF XY: 0.118

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 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

African (AFR) AF: 0.392 AC: 13120 AN: 33476

American (AMR) AF: 0.0692 AC: 3097 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0869 AC: 2271 AN: 26136

East Asian (EAS) AF: 0.00101 AC: 40 AN: 39700

South Asian (SAS) AF: 0.0893 AC: 7700 AN: 86240

European-Finnish (FIN) AF: 0.153 AC: 8153 AN: 53418

Middle Eastern (MID) AF: 0.113 AC: 651 AN: 5768

European-Non Finnish (NFE) AF: 0.127 AC: 141530 AN: 1111910

Other (OTH) AF: 0.126 AC: 7608 AN: 60394

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

African (AFR) AF: 0.374 AC: 15492 AN: 41416

American (AMR) AF: 0.114 AC: 1749 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0868 AC: 301 AN: 3466

East Asian (EAS) AF: 0.00232 AC: 12 AN: 5168

South Asian (SAS) AF: 0.0839 AC: 405 AN: 4826

European-Finnish (FIN) AF: 0.148 AC: 1561 AN: 10574

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

European-Non Finnish (NFE) AF: 0.129 AC: 8792 AN: 67974

Other (OTH) AF: 0.179 AC: 378 AN: 2112

Alfa AF: 0.141 Hom.: 6588

Bravo AF: 0.194

EpiCase AF: 0.127

EpiControl AF: 0.120

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
MetaRNN	Benign	0.0013	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.0
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.084
Sift	Benign	0.41	T
Sift4G	Benign	0.66	T
Varity_R		0.094
gMVP		0.091
Mutation Taster		=98/2	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs197414;

hg19: chr1-112309123;

COSMIC: COSV63778077;

COSMIC: COSV63778077;