2-15613283-G-A
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_004939.3(DDX1):c.1016G>A(p.Gly339Glu) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 1,601,780 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
DDX1
NM_004939.3 missense, splice_region
NM_004939.3 missense, splice_region
Scores
5
9
5
Splicing: ADA: 0.9741
1
1
Clinical Significance
Conservation
PhyloP100: 8.65
Genes affected
DDX1 (HGNC:2734): (DEAD-box helicase 1) 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 that acts as an ATP-dependent RNA helicase that has been found to promote coronaviruses replication. [provided by RefSeq, Aug 2021]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
High AC in GnomAdExome4 at 17 AD gene.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152098Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000696 AC: 17AN: 244104Hom.: 0 AF XY: 0.0000909 AC XY: 12AN XY: 131942
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GnomAD4 exome AF: 0.0000117 AC: 17AN: 1449682Hom.: 0 Cov.: 28 AF XY: 0.0000153 AC XY: 11AN XY: 721274
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152098Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74286
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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 | Feb 05, 2024 | The c.1016G>A (p.G339E) alteration is located in exon 14 (coding exon 14) of the DDX1 gene. This alteration results from a G to A substitution at nucleotide position 1016, causing the glycine (G) at amino acid position 339 to be replaced by a glutamic acid (E). 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
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T;T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;.;.
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;.;.
REVEL
Uncertain
Sift
Uncertain
D;D;.;.
Sift4G
Uncertain
D;D;D;D
Polyphen
D;D;.;.
Vest4
MutPred
Gain of catalytic residue at G339 (P = 0.0178);Gain of catalytic residue at G339 (P = 0.0178);.;.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at