chr22-38502810-T-C

Variant names:

• chr22-38502810-T-C
• rs12627803
• NM_006386.5:c.288-1530A>G

Variant summary

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

The NM_006386.5(DDX17):​c.288-1530A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0798 in 152,298 control chromosomes in the GnomAD database, including 656 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 0.080 (656 hom., cov: 32)
• Consequence: DDX17 NM_006386.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• Publications: 6 publications found

Genes affected

DDX17 (HGNC:2740): (DEAD-box helicase 17) 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 splicesosome 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 is an ATPase activated by a variety of RNA species, but not by dsDNA. This protein, and that encoded by DDX5 gene, are more closely related to each other than to any other member of the DEAD box family. This gene can encode multiple isoforms due to both alternative splicing and the use of alternative translation initiation codons, including a non-AUG (CUG) start codon. [provided by RefSeq, Apr 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006386.5. 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
	DDX17	NM_006386.5	MANE Select	c.288-1530A>G		intron	N/A	NP_006377.2
	DDX17	NM_001098504.2		c.288-1530A>G		intron	N/A	NP_001091974.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX17	ENST00000403230.3	TSL:1 MANE Select	c.288-1530A>G		intron	N/A	ENSP00000385536.2
	DDX17	ENST00000396821.8	TSL:1	c.288-1530A>G		intron	N/A	ENSP00000380033.4
	DDX17	ENST00000216019.11	TSL:1	n.345-1530A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0798 AC: 12142 AN: 152180 Hom.: 651 Cov.: 32

Gnomad AFR AF: 0.0211

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.0976

Gnomad ASJ AF: 0.0991

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0897

Gnomad OTH AF: 0.0831

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0798 AC: 12160 AN: 152298 Hom.: 656 Cov.: 32 AF XY: 0.0844 AC XY: 6282 AN XY: 74470

African (AFR) AF: 0.0210 AC: 875 AN: 41574

American (AMR) AF: 0.0978 AC: 1495 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0991 AC: 344 AN: 3472

East Asian (EAS) AF: 0.204 AC: 1056 AN: 5186

South Asian (SAS) AF: 0.138 AC: 666 AN: 4828

European-Finnish (FIN) AF: 0.126 AC: 1338 AN: 10606

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0897 AC: 6104 AN: 68018

Other (OTH) AF: 0.0898 AC: 190 AN: 2116

Alfa AF: 0.0818 Hom.: 1565

Bravo AF: 0.0717

Asia WGS AF: 0.156 AC: 545 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.56
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12627803; hg19: chr22-38898815;