2-15595524-T-C

Position:

• chr2-15595524-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_004939.3(DDX1):​c.103T>C​(p.Leu35=) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

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]

ACMG classification

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/exons	MANE	UniProt
DDX1	NM_004939.3	c.103T>C	p.Leu35=	synonymous_variant	3/26	ENST00000233084.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDX1	ENST00000233084.8	c.103T>C	p.Leu35=	synonymous_variant	3/26	1	NM_004939.3	P1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22329 AN: 152070 Hom.: 1994 Cov.: 32

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

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.: 30 AF XY: 0.195 AC XY: 140691 AN XY: 723216

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.: 32 AF XY: 0.145 AC XY: 10776 AN XY: 74416

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

Other links and lift over

dbSNP: rs2302929; hg19: chr2-15735648; COSMIC: COSV51838046; COSMIC: COSV51838046;