rs1991401

Positions:

• chr17-64506317-A-G
• chr17-64506317-A-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4 BA1

The NM_001320595.2(DDX5):​c.-143-55T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 1,500,118 control chromosomes in the GnomAD database, including 79,288 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 0.26 (6363 hom., cov: 30)
  • Exomes 𝑓: 0.32 (72925 hom.)
• Consequence: DDX5 NM_001320595.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.54

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.16).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDX5	NM_001320595.2	c.-143-55T>C		intron_variant
DDX5	NM_001320596.3	c.-143-55T>C		intron_variant
DDX5	XM_047435513.1	c.-143-55T>C		intron_variant
DDX5	NM_004396.5			upstream_gene_variant		ENST00000225792.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDX5	ENST00000225792.10			upstream_gene_variant		1	NM_004396.5	P1

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39509 AN: 151896 Hom.: 6348 Cov.: 30

Gnomad AFR AF: 0.0629

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.475

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.250

GnomAD4 exome AF: 0.322 AC: 434352 AN: 1348104 Hom.: 72925 Cov.: 40 AF XY: 0.326 AC XY: 215741 AN XY: 660780

Gnomad4 AFR exome AF: 0.0509

Gnomad4 AMR exome AF: 0.350

Gnomad4 ASJ exome AF: 0.222

Gnomad4 EAS exome AF: 0.370

Gnomad4 SAS exome AF: 0.470

Gnomad4 FIN exome AF: 0.370

Gnomad4 NFE exome AF: 0.319

Gnomad4 OTH exome AF: 0.310

GnomAD4 genome AF: 0.260 AC: 39534 AN: 152014 Hom.: 6363 Cov.: 30 AF XY: 0.267 AC XY: 19866 AN XY: 74274

Gnomad4 AFR AF: 0.0628

Gnomad4 AMR AF: 0.304

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.388

Gnomad4 SAS AF: 0.475

Gnomad4 FIN AF: 0.366

Gnomad4 NFE AF: 0.330

Gnomad4 OTH AF: 0.254

Alfa AF: 0.318 Hom.: 10630

Bravo AF: 0.241

Asia WGS AF: 0.406 AC: 1410 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.16
CADD	Benign	21
DANN	Benign	0.93

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: rs1991401; hg19: chr17-62502435;