chr17-63805105-A-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_203499.3(DDX42):​c.656A>G​(p.Asn219Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000422 in 1,611,424 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000045 ( 0 hom. )

Consequence

DDX42
NM_203499.3 missense

Scores

1
1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.56

Publications

0 publications found
Variant links:
Genes affected
DDX42 (HGNC:18676): (DEAD-box helicase 42) This gene encodes a member of the Asp-Glu-Ala-Asp (DEAD) box protein family. Members of this protein family are putative RNA helicases, and 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. Members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. Two transcript variants encoding the same protein have been identified for this gene. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2
High AC in GnomAdExome4 at 66 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DDX42NM_203499.3 linkc.656A>G p.Asn219Ser missense_variant Exon 7 of 18 ENST00000389924.7 NP_987095.1 Q86XP3-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DDX42ENST00000389924.7 linkc.656A>G p.Asn219Ser missense_variant Exon 7 of 18 5 NM_203499.3 ENSP00000374574.2 Q86XP3-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152216
Hom.:
0
Cov.:
32
show subpopulations
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000242
AC:
6
AN:
247830
AF XY:
0.0000374
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.0000997
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000443
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000452
AC:
66
AN:
1459208
Hom.:
0
Cov.:
30
AF XY:
0.0000469
AC XY:
34
AN XY:
725710
show subpopulations
African (AFR)
AF:
0.0000899
AC:
3
AN:
33376
American (AMR)
AF:
0.00
AC:
0
AN:
43998
Ashkenazi Jewish (ASJ)
AF:
0.0000383
AC:
1
AN:
26094
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39612
South Asian (SAS)
AF:
0.0000117
AC:
1
AN:
85176
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53374
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5760
European-Non Finnish (NFE)
AF:
0.0000549
AC:
61
AN:
1111492
Other (OTH)
AF:
0.00
AC:
0
AN:
60326
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.490
Heterozygous variant carriers
0
4
9
13
18
22
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
4
8
12
16
20
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152216
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74356
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
41454
American (AMR)
AF:
0.00
AC:
0
AN:
15278
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5208
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4828
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10616
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.0000294
AC:
2
AN:
68040
Other (OTH)
AF:
0.00
AC:
0
AN:
2094
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000203), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000756
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
May 21, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.656A>G (p.N219S) alteration is located in exon 8 (coding exon 6) of the DDX42 gene. This alteration results from a A to G substitution at nucleotide position 656, causing the asparagine (N) at amino acid position 219 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
0.061
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.59
CADD
Uncertain
24
DANN
Benign
0.93
DEOGEN2
Benign
0.028
T;T;T;.;T
Eigen
Benign
-0.025
Eigen_PC
Benign
0.20
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.97
.;.;D;D;D
M_CAP
Benign
0.0028
T
MetaRNN
Benign
0.13
T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.88
L;L;L;.;.
PhyloP100
5.6
PrimateAI
Benign
0.47
T
PROVEAN
Benign
-0.87
.;.;N;.;.
REVEL
Benign
0.074
Sift
Benign
0.71
.;.;T;.;.
Sift4G
Benign
0.36
T;T;T;T;T
Polyphen
0.0040
B;B;B;.;.
Vest4
0.23
MutPred
0.26
Gain of phosphorylation at N219 (P = 0.0797);Gain of phosphorylation at N219 (P = 0.0797);Gain of phosphorylation at N219 (P = 0.0797);.;.;
MVP
0.42
MPC
0.78
ClinPred
0.34
T
GERP RS
6.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.11
gMVP
0.23
Mutation Taster
=91/9
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.31
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.31
Position offset: 1

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

Publications

Other links and lift over

dbSNP: rs758688060; hg19: chr17-61882465; API