17-63800536-T-A

Position:

• chr17-63800536-T-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_203499.3(DDX42):​c.540T>A​(p.Asn180Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DDX42 NM_203499.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.472

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]

DDX42 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060157895).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX42	NM_203499.3	c.540T>A	p.Asn180Lys	missense_variant	6/18	ENST00000389924.7	NP_987095.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX42	ENST00000389924.7	c.540T>A	p.Asn180Lys	missense_variant	6/18	5	NM_203499.3	ENSP00000374574.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 10, 2024

The c.540T>A (p.N180K) alteration is located in exon 7 (coding exon 5) of the DDX42 gene. This alteration results from a T to A substitution at nucleotide position 540, causing the asparagine (N) at amino acid position 180 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	19
DANN	Benign	0.80
DEOGEN2	Benign	0.043	T;T;T;.;T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.54	D
LIST_S2	Uncertain	0.97	.;.;D;D;D
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.060	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	M;M;M;.;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.47	.;.;N;.;.
REVEL	Benign	0.013
Sift	Benign	0.45	.;.;T;.;.
Sift4G	Benign	0.79	T;T;T;T;T
Polyphen		0.14	B;B;B;.;.
Vest4		0.43
MutPred		0.34		Gain of ubiquitination at N180 (P = 0.0016);Gain of ubiquitination at N180 (P = 0.0016);Gain of ubiquitination at N180 (P = 0.0016);.;.;
MVP		0.54
MPC		1.2
ClinPred		0.059	T
GERP RS		0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.039
gMVP		0.46

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-61877896;