rs17569368

Variant names:

• chr1-111761169-A-T
• rs17569368
• NM_007204.5:c.962+44A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000369702.5(DDX20):​c.962+44A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0388 in 1,611,488 control chromosomes in the GnomAD database, including 1,458 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 0.036 (133 hom., cov: 33)
  • Exomes 𝑓: 0.039 (1325 hom.)
• Consequence: DDX20 ENST00000369702.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.525
• Publications: 8 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0668 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000369702.5. 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
	DDX20	NM_007204.5	MANE Select	c.962+44A>T		intron	N/A	NP_009135.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX20	ENST00000369702.5	TSL:1 MANE Select	c.962+44A>T		intron	N/A	ENSP00000358716.4
	DDX20	ENST00000475700.1	TSL:2	n.656A>T		non_coding_transcript_exon	Exon 2 of 3
	DDX20	ENST00000524894.2	TSL:2	n.651A>T		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.0356 AC: 5414 AN: 152218 Hom.: 131 Cov.: 33

Gnomad AFR AF: 0.0212

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0595

Gnomad ASJ AF: 0.0438

Gnomad EAS AF: 0.0724

Gnomad SAS AF: 0.0300

Gnomad FIN AF: 0.0299

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0372

Gnomad OTH AF: 0.0392

GnomAD2 exomes AF: 0.0477 AC: 11908 AN: 249606 AF XY: 0.0448

Gnomad AFR exome AF: 0.0180

Gnomad AMR exome AF: 0.107

Gnomad ASJ exome AF: 0.0457

Gnomad EAS exome AF: 0.0743

Gnomad FIN exome AF: 0.0332

Gnomad NFE exome AF: 0.0379

Gnomad OTH exome AF: 0.0532

GnomAD4 exome AF: 0.0391 AC: 57034 AN: 1459152 Hom.: 1325 Cov.: 32 AF XY: 0.0385 AC XY: 27965 AN XY: 725804

African (AFR) AF: 0.0190 AC: 634 AN: 33294

American (AMR) AF: 0.101 AC: 4490 AN: 44394

Ashkenazi Jewish (ASJ) AF: 0.0479 AC: 1249 AN: 26058

East Asian (EAS) AF: 0.0780 AC: 3088 AN: 39606

South Asian (SAS) AF: 0.0279 AC: 2394 AN: 85846

European-Finnish (FIN) AF: 0.0346 AC: 1843 AN: 53310

Middle Eastern (MID) AF: 0.0619 AC: 356 AN: 5754

European-Non Finnish (NFE) AF: 0.0365 AC: 40495 AN: 1110616

Other (OTH) AF: 0.0412 AC: 2485 AN: 60274

GnomAD4 genome AF: 0.0357 AC: 5431 AN: 152336 Hom.: 133 Cov.: 33 AF XY: 0.0350 AC XY: 2609 AN XY: 74488

African (AFR) AF: 0.0215 AC: 893 AN: 41590

American (AMR) AF: 0.0596 AC: 913 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0438 AC: 152 AN: 3468

East Asian (EAS) AF: 0.0728 AC: 378 AN: 5192

South Asian (SAS) AF: 0.0306 AC: 148 AN: 4830

European-Finnish (FIN) AF: 0.0299 AC: 318 AN: 10620

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0372 AC: 2527 AN: 68006

Other (OTH) AF: 0.0383 AC: 81 AN: 2114

Alfa AF: 0.0380 Hom.: 24

Bravo AF: 0.0391

Asia WGS AF: 0.0510 AC: 179 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	17
DANN	Benign	0.76
PhyloP100		0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=299/1	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: rs17569368; hg19: chr1-112303791; COSMIC: COSV63831602; COSMIC: COSV63831602;