1-111766501-C-A

Variant names:

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

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. 15/22 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 the same amino acid substitution has been previously reported as Likely benign in 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

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX20	NM_007204.5	c.2077C>A	p.Arg693Ser	missense_variant	Exon 11 of 11	ENST00000369702.5	NP_009135.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX20	ENST00000369702.5	c.2077C>A	p.Arg693Ser	missense_variant	Exon 11 of 11	1	NM_007204.5	ENSP00000358716.4

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

Gnomad4 AFR exome AF: 0.392 AC: 13120 AN: 33476

Gnomad4 AMR exome AF: 0.0692 AC: 3097 AN: 44724

Gnomad4 ASJ exome AF: 0.0869 AC: 2271 AN: 26136

Gnomad4 EAS exome AF: 0.00101 AC: 40 AN: 39700

Gnomad4 SAS exome AF: 0.0893 AC: 7700 AN: 86240

Gnomad4 FIN exome AF: 0.153 AC: 8153 AN: 53418

Gnomad4 NFE exome AF: 0.127 AC: 141530 AN: 1111910

Gnomad4 Remaining exome 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

Gnomad4 AFR AF: 0.374 AC: 0.374058 AN: 0.374058

Gnomad4 AMR AF: 0.114 AC: 0.114448 AN: 0.114448

Gnomad4 ASJ AF: 0.0868 AC: 0.0868436 AN: 0.0868436

Gnomad4 EAS AF: 0.00232 AC: 0.00232198 AN: 0.00232198

Gnomad4 SAS AF: 0.0839 AC: 0.0839204 AN: 0.0839204

Gnomad4 FIN AF: 0.148 AC: 0.147626 AN: 0.147626

Gnomad4 NFE AF: 0.129 AC: 0.129344 AN: 0.129344

Gnomad4 OTH AF: 0.179 AC: 0.178977 AN: 0.178977

Alfa AF: 0.141 Hom.: 6588

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;.
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
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

Publications

LitVar

Other links and lift over

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