chr17-64506317-A-G

Variant names:

• chr17-64506317-A-G
• rs1991401
• ENST00000578400.5:n.-198T>C

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4 BA1

The ENST00000578400.5(DDX5):​n.-198T>C variant causes a non coding transcript exon 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 ENST00000578400.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.54
• Publications: 51 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000578400.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX5	NM_001320595.2		c.-143-55T>C		intron	N/A	NP_001307524.1
	DDX5	NM_001320596.3		c.-143-55T>C		intron	N/A	NP_001307525.1
	DDX5	NM_004396.5	MANE Select	c.-198T>C		upstream_gene	N/A	NP_004387.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX5	ENST00000578400.5	TSL:5	n.-198T>C		non_coding_transcript_exon	Exon 1 of 5	ENSP00000463975.1
	DDX5	ENST00000578491.2	TSL:2	n.205T>C		non_coding_transcript_exon	Exon 1 of 12
	DDX5	ENST00000585317.2	TSL:2	n.183T>C		non_coding_transcript_exon	Exon 1 of 10

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

African (AFR) AF: 0.0509 AC: 1574 AN: 30898

American (AMR) AF: 0.350 AC: 11798 AN: 33730

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 5098 AN: 23002

East Asian (EAS) AF: 0.370 AC: 13039 AN: 35200

South Asian (SAS) AF: 0.470 AC: 34403 AN: 73274

European-Finnish (FIN) AF: 0.370 AC: 12309 AN: 33278

Middle Eastern (MID) AF: 0.282 AC: 1229 AN: 4352

European-Non Finnish (NFE) AF: 0.319 AC: 337525 AN: 1058302

Other (OTH) AF: 0.310 AC: 17377 AN: 56068

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

African (AFR) AF: 0.0628 AC: 2606 AN: 41528

American (AMR) AF: 0.304 AC: 4644 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 754 AN: 3466

East Asian (EAS) AF: 0.388 AC: 1999 AN: 5156

South Asian (SAS) AF: 0.475 AC: 2285 AN: 4806

European-Finnish (FIN) AF: 0.366 AC: 3859 AN: 10546

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.330 AC: 22432 AN: 67900

Other (OTH) AF: 0.254 AC: 536 AN: 2114

Alfa AF: 0.315 Hom.: 15165

Bravo AF: 0.241

Asia WGS AF: 0.406 AC: 1410 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.16
CADD	Benign	21
DANN	Benign	0.93
PhyloP100		3.5
PromoterAI		-0.22	Neutral
Mutation Taster		=298/2	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

Other links and lift over

dbSNP: rs1991401; hg19: chr17-62502435;