rs1140409

chr17-64500552-A-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 1P and 12B. PP2 BP4_Strong BA1

The NM_004396.5(DDX5):c.1438T>G(p.Ser480Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.059 in 1,612,270 control chromosomes in the GnomAD database, including 3,143 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 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 0.050 (264 hom., cov: 32)
  • Exomes 𝑓: 0.060 (2879 hom.)
• Consequence: DDX5 NM_004396.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.46

Genes affected

DDX5 (HGNC:2746): (DEAD-box helicase 5) This gene encodes a member of the DEAD box family of RNA helicases that are involved in a variety of cellular processes as a result of its role as an adaptor molecule, promoting interactions with a large number of other factors. This protein is involved in pathways that include the alteration of RNA structures, plays a role as a coregulator of transcription, a regulator of splicing, and in the processing of small noncoding RNAs. Members of this family contain nine conserved motifs, including the conserved Asp-Glu-Ala-Asp (DEAD) motif, important to ATP binding and hydrolysis as well as RNA binding and unwinding activities. Dysregulation of this gene may play a role in cancer development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2017]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• PP2: Missense variant where missense usually causes diseases, DDX5
• BP4: Computational evidence support a benign effect (MetaRNN=0.0014832616).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDX5	NM_004396.5	c.1438T>G	p.Ser480Ala	missense_variant	12/13	ENST00000225792.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDX5	ENST00000225792.10	c.1438T>G	p.Ser480Ala	missense_variant	12/13	1	NM_004396.5	P1

Frequencies

GnomAD3 genomes AF: 0.0498 AC: 7587 AN: 152220 Hom.: 264 Cov.: 32

Gnomad AFR AF: 0.0103

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.0409

Gnomad ASJ AF: 0.0879

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0341

Gnomad FIN AF: 0.0942

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0709

Gnomad OTH AF: 0.0545

GnomAD3 exomes AF: 0.0540 AC: 13463 AN: 249176 Hom.: 500 AF XY: 0.0558 AC XY: 7508 AN XY: 134616

Gnomad AFR exome AF: 0.00961

Gnomad AMR exome AF: 0.0260

Gnomad ASJ exome AF: 0.0874

Gnomad EAS exome AF: 0.000218

Gnomad SAS exome AF: 0.0343

Gnomad FIN exome AF: 0.0866

Gnomad NFE exome AF: 0.0732

Gnomad OTH exome AF: 0.0671

GnomAD4 exome AF: 0.0599 AC: 87467 AN: 1459932 Hom.: 2879 Cov.: 31 AF XY: 0.0601 AC XY: 43645 AN XY: 726208

Gnomad4 AFR exome AF: 0.00926

Gnomad4 AMR exome AF: 0.0271

Gnomad4 ASJ exome AF: 0.0869

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.0355

Gnomad4 FIN exome AF: 0.0882

Gnomad4 NFE exome AF: 0.0648

Gnomad4 OTH exome AF: 0.0580

GnomAD4 genome AF: 0.0498 AC: 7584 AN: 152338 Hom.: 264 Cov.: 32 AF XY: 0.0505 AC XY: 3760 AN XY: 74482

Gnomad4 AFR AF: 0.0102

Gnomad4 AMR AF: 0.0409

Gnomad4 ASJ AF: 0.0879

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0344

Gnomad4 FIN AF: 0.0942

Gnomad4 NFE AF: 0.0709

Gnomad4 OTH AF: 0.0539

Alfa AF: 0.0655 Hom.: 791

Bravo AF: 0.0429

TwinsUK AF: 0.0564 AC: 209

ALSPAC AF: 0.0589 AC: 227

ESP6500AA AF: 0.0116 AC: 51

ESP6500EA AF: 0.0715 AC: 615

ExAC AF: 0.0561 AC: 6815

Asia WGS AF: 0.0130 AC: 44 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.53
Cadd	Uncertain	23
Dann	Benign	0.93
DEOGEN2	Benign	0.089	T;.;T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.027
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.57	T;T;T
MetaRNN	Benign	0.0015	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L;.;.
MutationTaster	Benign	0.94	D;D;D
PrimateAI	Uncertain	0.54	T
REVEL	Benign	0.17
Sift4G	Benign	0.21	T;T;T
Polyphen		0.024	B;.;.
Vest4		0.080
ClinPred		0.014	T
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.096
gMVP		0.29

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: rs1140409; hg19: chr17-62496670;