Genetic Variant DDX1:p.Leu35Leu (chr2-15595524-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_004939.3(DDX1):c.103T>C(p.Leu35Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 1,604,936 control chromosomes in the GnomAD database, including 31,237 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.15 ( 1991 hom., cov: 32)

Exomes 𝑓: 0.19 ( 29246 hom. )

Consequence

DDX1
NM_004939.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.08

Variant links:

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]

DDX1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP7

Synonymous conserved (PhyloP=-1.09 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX1	NM_004939.3 link	c.103T>C	p.Leu35Leu	synonymous_variant	Exon 3 of 26	ENST00000233084.8	NP_004930.1	Q92499-1A3RJH1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX1	ENST00000233084.8 link	c.103T>C	p.Leu35Leu	synonymous_variant	Exon 3 of 26	1	NM_004939.3	ENSP00000233084.3		Q92499-1

Frequencies

GnomAD3 genomes

AF:

0.147

AC:

22329

AN:

152070

Hom.:

1994

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0587

Gnomad AMI

AF:

0.126

Gnomad AMR

AF:

0.142

Gnomad ASJ

AF:

0.112

Gnomad EAS

AF:

0.372

Gnomad SAS

AF:

0.212

Gnomad FIN

AF:

0.112

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.187

Gnomad OTH

AF:

0.145

GnomAD3 exomes

AF:

0.180

AC:

45107

AN:

251248

Hom.:

4693

AF XY:

0.183

AC XY:

24835

AN XY:

135778

show subpopulations

Gnomad AFR exome

AF:

0.0571

Gnomad AMR exome

AF:

0.140

Gnomad ASJ exome

AF:

0.117

Gnomad EAS exome

AF:

0.378

Gnomad SAS exome

AF:

0.200

Gnomad FIN exome

AF:

0.117

Gnomad NFE exome

AF:

0.189

Gnomad OTH exome

AF:

0.173

GnomAD4 exome

AF:

0.194

AC:

281632

AN:

1452748

Hom.:

29246

Cov.:

AF XY:

0.195

AC XY:

140691

AN XY:

723216

show subpopulations

Gnomad4 AFR exome

AF:

0.0489

Gnomad4 AMR exome

AF:

0.139

Gnomad4 ASJ exome

AF:

0.114

Gnomad4 EAS exome

AF:

0.371

Gnomad4 SAS exome

AF:

0.198

Gnomad4 FIN exome

AF:

0.125

Gnomad4 NFE exome

AF:

0.200

Gnomad4 OTH exome

AF:

0.185

GnomAD4 genome

AF:

0.147

AC:

22326

AN:

152188

Hom.:

1991

Cov.:

AF XY:

0.145

AC XY:

10776

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.0587

Gnomad4 AMR

AF:

0.142

Gnomad4 ASJ

AF:

0.112

Gnomad4 EAS

AF:

0.371

Gnomad4 SAS

AF:

0.212

Gnomad4 FIN

AF:

0.112

Gnomad4 NFE

AF:

0.187

Gnomad4 OTH

AF:

0.147

Alfa

AF:

0.168

Hom.:

2805

Bravo

AF:

0.146

Asia WGS

AF:

0.281

AC:

975

AN:

3478

EpiCase

AF:

0.190

EpiControl

AF:

0.194

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.2

DANN

Benign

0.59

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over