DDX41 p.Arg369*

Variant names:

• chr5-177514824-CG-TA
• NM_016222.4:c.811_812delCGinsTA
• DDX41 p.Arg271*

Your query was ambiguous. Multiple possible variants found:

• chr5-177514824-CG-TA
• chr5-177513478-G-A
• chr5-177513751-G-A

Variant summary

Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PVS1

The NM_016222.4(DDX41):​c.811_812delCGinsTA​(p.Arg271*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R271R) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DDX41 NM_016222.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.43
• Publications: 0 publications found

Genes affected

DDX41 (HGNC:18674): (DEAD-box helicase 41) 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 the DEAD box protein family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. The protein encoded by this gene is a member of the DEAD box protein family and interacts with several spliceosomal proteins. In addition, the encoded protein may recognize the bacterial second messengers cyclic di-GMP and cyclic di-AMP, resulting in the induction of genes involved in the innate immune response. [provided by RefSeq, Jan 2017]

DDX41 Gene-Disease associations (from GenCC):

• DDX41-related hematologic malignancy predisposition syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), ClinGen
• acromesomelic dysplasia

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_pathogenic. The variant received 8 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016222.4. 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
	DDX41	NM_016222.4	MANE Select	c.811_812delCGinsTA	p.Arg271*	stop_gained	N/A	NP_057306.2
	DDX41	NM_001321732.2		c.433_434delCGinsTA	p.Arg145*	stop_gained	N/A	NP_001308661.1	B3KRK2
	DDX41	NM_001321830.2		c.433_434delCGinsTA	p.Arg145*	stop_gained	N/A	NP_001308759.1	B3KRK2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX41	ENST00000330503.12	TSL:1 MANE Select	c.811_812delCGinsTA	p.Arg271*	stop_gained	N/A	ENSP00000330349.8	Q9UJV9
	DDX41	ENST00000507955.6	TSL:1	n.811_812delCGinsTA		non_coding_transcript_exon	Exon 9 of 17	ENSP00000422753.2	A0A499FJW5
	DDX41	ENST00000904584.1		c.832_833delCGinsTA	p.Arg278*	stop_gained	N/A	ENSP00000574643.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr5-176941825;