chr17-63792450-A-C

Position:

• chr17-63792450-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_203499.3(DDX42):​c.260A>C​(p.Asp87Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: DDX42 NM_203499.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.14

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19845632).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX42	NM_203499.3	c.260A>C	p.Asp87Ala	missense_variant	3/18	ENST00000389924.7	NP_987095.1
DDX42	NM_007372.3	c.260A>C	p.Asp87Ala	missense_variant	4/19		NP_031398.2
DDX42	XM_047435281.1	c.260A>C	p.Asp87Ala	missense_variant	5/20		XP_047291237.1
DDX42	XM_047435282.1	c.260A>C	p.Asp87Ala	missense_variant	6/21		XP_047291238.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX42	ENST00000389924.7	c.260A>C	p.Asp87Ala	missense_variant	3/18	5	NM_203499.3	ENSP00000374574.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461002 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726780

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000757

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Jan 18, 2022

The c.260A>C (p.D87A) alteration is located in exon 4 (coding exon 2) of the DDX42 gene. This alteration results from a A to C substitution at nucleotide position 260, causing the aspartic acid (D) at amino acid position 87 to be replaced by an alanine (A). 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	Uncertain	0.49
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	25
DANN	Benign	0.94
DEOGEN2	Benign	0.067	.;T;T;T
Eigen	Benign	0.072
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.87	D;.;.;T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.20	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	.;L;L;L
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.3	.;.;.;N
REVEL	Benign	0.12
Sift	Uncertain	0.012	.;.;.;D
Sift4G	Uncertain	0.030	D;T;T;T
Polyphen		0.043	.;B;B;B
Vest4		0.29, 0.29
MutPred		0.14		Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);
MVP		0.44
MPC		1.2
ClinPred		0.68	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.096
gMVP		0.42

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

LitVar

Other links and lift over

dbSNP: rs2039640108; hg19: chr17-61869810;