rs16947824

Positions:

• chr17-64505387-G-A
• chr17-64505387-G-T

Variant summary

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

The NM_004396.5(DDX5):​c.45-545C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0427 in 467,866 control chromosomes in the GnomAD database, including 667 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.050 (298 hom., cov: 33)
  • Exomes 𝑓: 0.039 (369 hom.)
• Consequence: DDX5 NM_004396.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.335

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX5	NM_004396.5	c.45-545C>T		intron_variant		ENST00000225792.10	NP_004387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX5	ENST00000225792.10	c.45-545C>T		intron_variant		1	NM_004396.5	ENSP00000225792	P1

Frequencies

GnomAD3 genomes AF: 0.0498 AC: 7570 AN: 152146 Hom.: 299 Cov.: 33

Gnomad AFR AF: 0.0401

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.0435

Gnomad EAS AF: 0.0327

Gnomad SAS AF: 0.0350

Gnomad FIN AF: 0.0446

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0404

Gnomad OTH AF: 0.0445

GnomAD4 exome AF: 0.0394 AC: 12430 AN: 315602 Hom.: 369 Cov.: 0 AF XY: 0.0388 AC XY: 6387 AN XY: 164546

Gnomad4 AFR exome AF: 0.0376

Gnomad4 AMR exome AF: 0.125

Gnomad4 ASJ exome AF: 0.0338

Gnomad4 EAS exome AF: 0.0316

Gnomad4 SAS exome AF: 0.0309

Gnomad4 FIN exome AF: 0.0428

Gnomad4 NFE exome AF: 0.0363

Gnomad4 OTH exome AF: 0.0406

GnomAD4 genome AF: 0.0497 AC: 7567 AN: 152264 Hom.: 298 Cov.: 33 AF XY: 0.0526 AC XY: 3919 AN XY: 74470

Gnomad4 AFR AF: 0.0400

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.0435

Gnomad4 EAS AF: 0.0326

Gnomad4 SAS AF: 0.0352

Gnomad4 FIN AF: 0.0446

Gnomad4 NFE AF: 0.0404

Gnomad4 OTH AF: 0.0440

Alfa AF: 0.0388 Hom.: 127

Bravo AF: 0.0523

Asia WGS AF: 0.0340 AC: 118 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.9
DANN	Benign	0.84

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: rs16947824; hg19: chr17-62501505;