22-38488031-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_006386.5(DDX17):​c.1532G>A​(p.Arg511His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 12/19 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 32)
Failed GnomAD Quality Control

Consequence

DDX17
NM_006386.5 missense

Scores

16
2
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.84
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.984

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DDX17NM_006386.5 linkc.1532G>A p.Arg511His missense_variant Exon 12 of 13 ENST00000403230.3 NP_006377.2 Q92841-4
DDX17NM_001098504.2 linkc.1532G>A p.Arg511His missense_variant Exon 12 of 13 NP_001091974.1 A0A5H1ZRQ2Q59F66

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DDX17ENST00000403230.3 linkc.1532G>A p.Arg511His missense_variant Exon 12 of 13 1 NM_006386.5 ENSP00000385536.2 Q92841-4A0A1X7SBZ2

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
0
AN:
152188
Hom.:
0
Cov.:
32
FAILED QC
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
152306
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74470
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Sep 10, 2024
GeneDx
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Variants in candidate genes are classified as variants of uncertain significance in accordance with ACMG guidelines (PMID: 25741868) -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.53
D
BayesDel_noAF
Pathogenic
0.53
CADD
Pathogenic
33
DANN
Pathogenic
1.0
DEOGEN2
Pathogenic
0.88
.;.;D;.
Eigen
Pathogenic
1.1
Eigen_PC
Pathogenic
0.96
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.95
.;D;D;D
M_CAP
Pathogenic
0.40
D
MetaRNN
Pathogenic
0.98
D;D;D;D
MetaSVM
Pathogenic
1.1
D
MutationAssessor
Pathogenic
4.3
.;.;H;.
PrimateAI
Pathogenic
0.86
D
PROVEAN
Pathogenic
-4.7
D;D;.;.
REVEL
Pathogenic
0.95
Sift
Pathogenic
0.0
D;D;.;.
Sift4G
Pathogenic
0.0010
D;D;.;.
MutPred
0.92
Loss of MoRF binding (P = 0.009);Loss of MoRF binding (P = 0.009);Loss of MoRF binding (P = 0.009);Loss of MoRF binding (P = 0.009);
MVP
0.99
ClinPred
1.0
D
GERP RS
5.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.76
gMVP
0.99

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-38884036; COSMIC: COSV53249855; COSMIC: COSV53249855; API