10-68901404-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024045.2(DDX50):ā€‹c.20G>Cā€‹(p.Trp7Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000242 in 1,566,678 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00014 ( 0 hom., cov: 32)
Exomes š‘“: 0.00025 ( 1 hom. )

Consequence

DDX50
NM_024045.2 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.00
Variant links:
Genes affected
DDX50 (HGNC:17906): (DExD-box helicase 50) 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 DEAD box protein family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box enzyme that may be involved in ribosomal RNA synthesis or processing. This gene and DDX21, also called RH-II/GuA, have similar genomic structures and are in tandem orientation on chromosome 10, suggesting that the two genes arose by gene duplication in evolution. This gene has pseudogenes on chromosomes 2, 3 and 4. Alternative splicing of this gene generates multiple transcript variants, but the full length nature of all the other variants but one has not been defined. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.05566874).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DDX50NM_024045.2 linkuse as main transcriptc.20G>C p.Trp7Ser missense_variant 1/15 ENST00000373585.8 NP_076950.1 Q9BQ39
DDX50XM_011540144.3 linkuse as main transcriptc.-230G>C 5_prime_UTR_variant 1/16 XP_011538446.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DDX50ENST00000373585.8 linkuse as main transcriptc.20G>C p.Trp7Ser missense_variant 1/151 NM_024045.2 ENSP00000362687.3 Q9BQ39
DDX50ENST00000471475.1 linkuse as main transcriptn.20G>C non_coding_transcript_exon_variant 1/65 ENSP00000474314.1 S4R3G6
DDX50ENST00000483593.5 linkuse as main transcriptn.20G>C non_coding_transcript_exon_variant 1/73 ENSP00000474785.1 S4R3V4

Frequencies

GnomAD3 genomes
AF:
0.000145
AC:
22
AN:
152236
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000482
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:
0.0000941
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000279
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000185
AC:
33
AN:
178216
Hom.:
0
AF XY:
0.000168
AC XY:
16
AN XY:
95300
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000381
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000412
Gnomad OTH exome
AF:
0.000212
GnomAD4 exome
AF:
0.000252
AC:
357
AN:
1414442
Hom.:
1
Cov.:
30
AF XY:
0.000259
AC XY:
181
AN XY:
699586
show subpopulations
Gnomad4 AFR exome
AF:
0.0000313
Gnomad4 AMR exome
AF:
0.0000797
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000315
Gnomad4 OTH exome
AF:
0.000171
GnomAD4 genome
AF:
0.000145
AC:
22
AN:
152236
Hom.:
0
Cov.:
32
AF XY:
0.000148
AC XY:
11
AN XY:
74386
show subpopulations
Gnomad4 AFR
AF:
0.0000482
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000941
Gnomad4 NFE
AF:
0.000279
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000223
Hom.:
0
Bravo
AF:
0.000140
ExAC
AF:
0.000193
AC:
23

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 10, 2024The c.20G>C (p.W7S) alteration is located in exon 1 (coding exon 1) of the DDX50 gene. This alteration results from a G to C substitution at nucleotide position 20, causing the tryptophan (W) at amino acid position 7 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.21
CADD
Pathogenic
26
DANN
Benign
0.96
DEOGEN2
Benign
0.044
T;T
Eigen
Benign
-0.43
Eigen_PC
Benign
-0.15
FATHMM_MKL
Benign
0.28
N
LIST_S2
Benign
0.80
T;T
M_CAP
Benign
0.0043
T
MetaRNN
Benign
0.056
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
L;.
PrimateAI
Pathogenic
0.80
D
PROVEAN
Benign
0.71
N;.
REVEL
Benign
0.17
Sift
Benign
0.94
T;.
Sift4G
Benign
0.74
T;D
Polyphen
0.012
B;.
Vest4
0.63
MVP
0.46
MPC
1.6
ClinPred
0.24
T
GERP RS
4.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.18
gMVP
0.079

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs530795940; hg19: chr10-70661160; COSMIC: COSV101007211; API