2-15595524-T-C

Variant names:

• chr2-15595524-T-C
• rs2302929
• NM_004939.3:c.103T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 20 publications found

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

Our verdict: Benign. The variant received -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	c.103T>C	p.Leu35Leu	synonymous_variant	Exon 3 of 26	ENST00000233084.8	NP_004930.1

Ensembl

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

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

GnomAD2 exomes AF: 0.180 AC: 45107 AN: 251248 AF XY: 0.183

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 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

African (AFR) AF: 0.0489 AC: 1634 AN: 33406

American (AMR) AF: 0.139 AC: 6231 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 2975 AN: 26074

East Asian (EAS) AF: 0.371 AC: 14689 AN: 39582

South Asian (SAS) AF: 0.198 AC: 17015 AN: 86022

European-Finnish (FIN) AF: 0.125 AC: 6680 AN: 53402

Middle Eastern (MID) AF: 0.117 AC: 674 AN: 5762

European-Non Finnish (NFE) AF: 0.200 AC: 220642 AN: 1103740

Other (OTH) AF: 0.185 AC: 11092 AN: 60066

GnomAD4 genome AF: 0.147 AC: 22326 AN: 152188 Hom.: 1991 Cov.: 32 AF XY: 0.145 AC XY: 10776 AN XY: 74416

African (AFR) AF: 0.0587 AC: 2437 AN: 41548

American (AMR) AF: 0.142 AC: 2173 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 388 AN: 3468

East Asian (EAS) AF: 0.371 AC: 1918 AN: 5172

South Asian (SAS) AF: 0.212 AC: 1020 AN: 4820

European-Finnish (FIN) AF: 0.112 AC: 1188 AN: 10600

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.187 AC: 12728 AN: 67980

Other (OTH) AF: 0.147 AC: 310 AN: 2110

Alfa AF: 0.166 Hom.: 3350

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
PhyloP100		-1.1
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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