1-111763005-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_007204.5(DDX20):c.1310C>T(p.Pro437Leu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000482 in 1,602,864 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00049 ( 0 hom. )
Consequence
DDX20
NM_007204.5 missense, splice_region
NM_007204.5 missense, splice_region
Scores
4
9
6
Splicing: ADA: 0.9998
2
Clinical Significance
Conservation
PhyloP100: 5.38
Genes affected
DDX20 (HGNC:2743): (DEAD-box helicase 20) 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 family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box protein, which has an ATPase activity and is a component of the survival of motor neurons (SMN) complex. This protein interacts directly with SMN, the spinal muscular atrophy gene product, and may play a catalytic role in the function of the SMN complex on RNPs. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DDX20 | NM_007204.5 | c.1310C>T | p.Pro437Leu | missense_variant, splice_region_variant | 10/11 | ENST00000369702.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DDX20 | ENST00000369702.5 | c.1310C>T | p.Pro437Leu | missense_variant, splice_region_variant | 10/11 | 1 | NM_007204.5 | P2 |
Frequencies
GnomAD3 genomes AF: 0.000388 AC: 59AN: 152072Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000300 AC: 75AN: 250072Hom.: 0 AF XY: 0.000252 AC XY: 34AN XY: 135138
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GnomAD4 exome AF: 0.000492 AC: 714AN: 1450792Hom.: 0 Cov.: 30 AF XY: 0.000493 AC XY: 356AN XY: 722418
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GnomAD4 genome AF: 0.000388 AC: 59AN: 152072Hom.: 0 Cov.: 32 AF XY: 0.000296 AC XY: 22AN XY: 74284
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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 | Jun 21, 2021 | The c.1310C>T (p.P437L) alteration is located in exon 10 (coding exon 10) of the DDX20 gene. This alteration results from a C to T substitution at nucleotide position 1310, causing the proline (P) at amino acid position 437 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Benign
D;D
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at