Variant chr17-63812007-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_203499.3(DDX42):c.1474C>A(p.Leu492Met) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DDX42
NM_203499.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.09

Variant links:

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 links:

DDX42 (HGNC:):

DDX42 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX42	NM_203499.3 linkuse as main transcript	c.1474C>A	p.Leu492Met	missense_variant	14/18	ENST00000389924.7	NP_987095.1	Q86XP3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX42	ENST00000389924.7 linkuse as main transcript	c.1474C>A	p.Leu492Met	missense_variant	14/18	5	NM_203499.3	ENSP00000374574.2		Q86XP3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

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.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 11, 2022

The c.1474C>A (p.L492M) alteration is located in exon 15 (coding exon 13) of the DDX42 gene. This alteration results from a C to A substitution at nucleotide position 1474, causing the leucine (L) at amino acid position 492 to be replaced by a methionine (M). 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

Benign

0.22

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Benign

-0.35

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.18

T;T;T;.;T

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.92

.;.;D;D;D

M_CAP

Benign

0.033

MetaRNN

Uncertain

0.60

D;D;D;D;D

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.6

M;M;M;.;.

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-1.7

.;.;N;.;N

REVEL

Benign

0.21

Sift

Uncertain

0.029

.;.;D;.;D

Sift4G

Uncertain

0.043

D;D;D;D;D

Polyphen

0.97

D;D;D;.;.

Vest4

0.62

MutPred

0.57

Gain of MoRF binding (P = 0.0744);Gain of MoRF binding (P = 0.0744);Gain of MoRF binding (P = 0.0744);.;.;

MVP

0.47

MPC

2.0

ClinPred

0.89

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.18

gMVP

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over