chr17-63815609-A-T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_203499.3(DDX42):c.1949A>T(p.Lys650Met) variant causes a missense change. The variant allele was found at a frequency of 0.000396 in 1,614,040 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00022 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00041 ( 1 hom. )
Consequence
DDX42
NM_203499.3 missense
NM_203499.3 missense
Scores
3
4
8
Clinical Significance
Conservation
PhyloP100: 6.18
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, DDX42
BP4
?
Computational evidence support a benign effect (MetaRNN=0.1463398).
BS2
?
High AC in GnomAd at 34 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DDX42 | NM_203499.3 | c.1949A>T | p.Lys650Met | missense_variant | 16/18 | ENST00000389924.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DDX42 | ENST00000389924.7 | c.1949A>T | p.Lys650Met | missense_variant | 16/18 | 5 | NM_203499.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000223 AC: 34AN: 152188Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000187 AC: 47AN: 251390Hom.: 0 AF XY: 0.000206 AC XY: 28AN XY: 135864
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GnomAD4 exome AF: 0.000414 AC: 605AN: 1461734Hom.: 1 Cov.: 30 AF XY: 0.000391 AC XY: 284AN XY: 727180
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GnomAD4 genome ? AF: 0.000223 AC: 34AN: 152306Hom.: 1 Cov.: 32 AF XY: 0.000255 AC XY: 19AN XY: 74478
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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 submitter | clinical testing | Ambry Genetics | Apr 12, 2022 | The c.1949A>T (p.K650M) alteration is located in exon 17 (coding exon 15) of the DDX42 gene. This alteration results from a A to T substitution at nucleotide position 1949, causing the lysine (K) at amino acid position 650 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;T;T;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L;.;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Pathogenic
T
Sift4G
Uncertain
D;D;D;D;D
Polyphen
D;D;D;.;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at