rs197412

Positions:

• chr1-111766331-T-C
• chr1-111766331-T-G

Variant summary

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

The NM_007204.5(DDX20):​c.1907T>C​(p.Ile636Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 1,613,432 control chromosomes in the GnomAD database, including 139,825 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.48 (18790 hom., cov: 32)
  • Exomes 𝑓: 0.40 (121035 hom.)
• Consequence: DDX20 NM_007204.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.93

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]

DDX20 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.599391E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX20	NM_007204.5	c.1907T>C	p.Ile636Thr	missense_variant	11/11	ENST00000369702.5	NP_009135.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX20	ENST00000369702.5	c.1907T>C	p.Ile636Thr	missense_variant	11/11	1	NM_007204.5	ENSP00000358716.4

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72961 AN: 151948 Hom.: 18749 Cov.: 32

Gnomad AFR AF: 0.681

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.475

GnomAD3 exomes AF: 0.426 AC: 106929 AN: 250918 Hom.: 23831 AF XY: 0.413 AC XY: 56028 AN XY: 135604

Gnomad AFR exome AF: 0.688

Gnomad AMR exome AF: 0.530

Gnomad ASJ exome AF: 0.357

Gnomad EAS exome AF: 0.345

Gnomad SAS exome AF: 0.338

Gnomad FIN exome AF: 0.452

Gnomad NFE exome AF: 0.396

Gnomad OTH exome AF: 0.411

GnomAD4 exome AF: 0.402 AC: 587222 AN: 1461366 Hom.: 121035 Cov.: 46 AF XY: 0.399 AC XY: 289877 AN XY: 726986

Gnomad4 AFR exome AF: 0.698

Gnomad4 AMR exome AF: 0.523

Gnomad4 ASJ exome AF: 0.356

Gnomad4 EAS exome AF: 0.356

Gnomad4 SAS exome AF: 0.337

Gnomad4 FIN exome AF: 0.463

Gnomad4 NFE exome AF: 0.393

Gnomad4 OTH exome AF: 0.403

GnomAD4 genome AF: 0.481 AC: 73068 AN: 152066 Hom.: 18790 Cov.: 32 AF XY: 0.477 AC XY: 35466 AN XY: 74324

Gnomad4 AFR AF: 0.682

Gnomad4 AMR AF: 0.462

Gnomad4 ASJ AF: 0.351

Gnomad4 EAS AF: 0.349

Gnomad4 SAS AF: 0.326

Gnomad4 FIN AF: 0.448

Gnomad4 NFE AF: 0.398

Gnomad4 OTH AF: 0.473

Alfa AF: 0.409 Hom.: 25500

Bravo AF: 0.492

TwinsUK AF: 0.393 AC: 1456

ALSPAC AF: 0.388 AC: 1497

ESP6500AA AF: 0.670 AC: 2950

ESP6500EA AF: 0.389 AC: 3345

ExAC AF: 0.427 AC: 51820

Asia WGS AF: 0.349 AC: 1219 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
AlphaMissense	Benign	0.049
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	11
DANN	Benign	0.68
DEOGEN2	Benign	0.045	T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.092	T;T
MetaRNN	Benign	0.0000026	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-1.8	N;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.49	N;N
REVEL	Benign	0.12
Sift	Benign	0.65	T;T
Sift4G	Benign	0.41	T;T
Polyphen		0.0	B;B
Vest4		0.035
MPC		0.10
ClinPred		0.0037	T
GERP RS		3.9
Varity_R		0.013
gMVP		0.074

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: rs197412; hg19: chr1-112308953; COSMIC: COSV63780126; COSMIC: COSV63780126;