chr10-68906925-T-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.302T>Cā€‹(p.Ile101Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,602,308 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000020 ( 0 hom., cov: 33)
Exomes š‘“: 0.000010 ( 0 hom. )

Consequence

DDX50
NM_024045.2 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.12
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=0.05093375).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DDX50NM_024045.2 linkuse as main transcriptc.302T>C p.Ile101Thr missense_variant 2/15 ENST00000373585.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DDX50ENST00000373585.8 linkuse as main transcriptc.302T>C p.Ile101Thr missense_variant 2/151 NM_024045.2 P1
DDX50ENST00000471475.1 linkuse as main transcriptc.*258T>C 3_prime_UTR_variant, NMD_transcript_variant 3/65
DDX50ENST00000483593.5 linkuse as main transcriptc.*236T>C 3_prime_UTR_variant, NMD_transcript_variant 3/73

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152156
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000724
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
GnomAD3 exomes
AF:
0.00000836
AC:
2
AN:
239330
Hom.:
0
AF XY:
0.00000773
AC XY:
1
AN XY:
129384
show subpopulations
Gnomad AFR exome
AF:
0.000127
Gnomad AMR exome
AF:
0.00
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000103
AC:
15
AN:
1450152
Hom.:
0
Cov.:
31
AF XY:
0.00000971
AC XY:
7
AN XY:
721016
show subpopulations
Gnomad4 AFR exome
AF:
0.000185
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000121
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000631
Gnomad4 OTH exome
AF:
0.0000167
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152156
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74338
show subpopulations
Gnomad4 AFR
AF:
0.0000724
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
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000113
ExAC
AF:
0.0000165
AC:
2

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 GeneticsSep 14, 2022The c.302T>C (p.I101T) alteration is located in exon 2 (coding exon 2) of the DDX50 gene. This alteration results from a T to C substitution at nucleotide position 302, causing the isoleucine (I) at amino acid position 101 to be replaced by a threonine (T). 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
0.054
BayesDel_addAF
Benign
-0.44
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
18
DANN
Benign
0.79
DEOGEN2
Benign
0.029
T;T
Eigen
Benign
-0.39
Eigen_PC
Benign
-0.17
FATHMM_MKL
Benign
0.65
D
LIST_S2
Benign
0.85
D;D
M_CAP
Benign
0.0042
T
MetaRNN
Benign
0.051
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.61
N;.
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.40
T
PROVEAN
Benign
0.26
N;.
REVEL
Benign
0.093
Sift
Benign
0.72
T;.
Sift4G
Benign
0.63
T;T
Polyphen
0.0010
B;.
Vest4
0.14
MutPred
0.24
Gain of phosphorylation at I101 (P = 0.0157);.;
MVP
0.40
MPC
0.63
ClinPred
0.062
T
GERP RS
3.9
Varity_R
0.038
gMVP
0.15

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: rs777281899; hg19: chr10-70666681; API