rs2665840

Variant names:

• chr17-63795947-A-G
• rs2665840
• NM_203499.3:c.373-2091A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_203499.3(DDX42):​c.373-2091A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 152,072 control chromosomes in the GnomAD database, including 8,599 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 0.32 (8599 hom., cov: 32)
• Consequence: DDX42 NM_203499.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.146
• Publications: 18 publications found

Genes affected

DDX42 (HGNC:18676): (DEAD-box helicase 42) This gene encodes a member of the Asp-Glu-Ala-Asp (DEAD) box protein family. Members of this protein family are putative RNA helicases, and 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. Members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. Two transcript variants encoding the same protein have been identified for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203499.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX42	NM_203499.3	MANE Select	c.373-2091A>G		intron	N/A	NP_987095.1	Q86XP3-1
	DDX42	NM_007372.3		c.373-2091A>G		intron	N/A	NP_031398.2	Q86XP3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX42	ENST00000389924.7	TSL:5 MANE Select	c.373-2091A>G		intron	N/A	ENSP00000374574.2	Q86XP3-1
	DDX42	ENST00000578681.5	TSL:1	c.373-2091A>G		intron	N/A	ENSP00000464050.1	Q86XP3-1
	DDX42	ENST00000583590.5	TSL:5	c.373-2091A>G		intron	N/A	ENSP00000463561.1	Q86XP3-1

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48903 AN: 151954 Hom.: 8588 Cov.: 32

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.311

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.322 AC: 48931 AN: 152072 Hom.: 8599 Cov.: 32 AF XY: 0.332 AC XY: 24673 AN XY: 74342

African (AFR) AF: 0.209 AC: 8690 AN: 41492

American (AMR) AF: 0.388 AC: 5923 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 914 AN: 3468

East Asian (EAS) AF: 0.523 AC: 2706 AN: 5174

South Asian (SAS) AF: 0.576 AC: 2774 AN: 4816

European-Finnish (FIN) AF: 0.438 AC: 4631 AN: 10564

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.329 AC: 22360 AN: 67978

Other (OTH) AF: 0.313 AC: 662 AN: 2112

Alfa AF: 0.336 Hom.: 6261

Bravo AF: 0.309

Asia WGS AF: 0.525 AC: 1821 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.43
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2665840; hg19: chr17-61873307;