Genetic Variant DDX20:p.Ala7Pro (chr1-111755943-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_007204.5(DDX20):c.19G>C(p.Ala7Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000701 in 1,426,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A7S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

DDX20
NM_007204.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.444

Publications

0 publications found

Variant links:

Genes affected

DDX20 (HGNC:2743): (DEAD-box helicase 20) 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 this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box protein, which has an ATPase activity and is a component of the survival of motor neurons (SMN) complex. This protein interacts directly with SMN, the spinal muscular atrophy gene product, and may play a catalytic role in the function of the SMN complex on RNPs. [provided by RefSeq, Jul 2008]

DDX20 links:

INKA2 (HGNC:28045): (inka box actin regulator 2) Enables protein kinase binding activity. Predicted to be involved in negative regulation of catalytic activity. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

INKA2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0640921).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX20	NM_007204.5 link	c.19G>C	p.Ala7Pro	missense_variant	Exon 1 of 11	ENST00000369702.5	NP_009135.4	Q9UHI6-1Q9H4N4
INKA2	NM_198926.2 link	c.-231C>G		upstream_gene_variant			NP_945120.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX20	ENST00000369702.5 link	c.19G>C	p.Ala7Pro	missense_variant	Exon 1 of 11	1	NM_007204.5	ENSP00000358716.4		Q9UHI6-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.01e-7

AC:

AN:

1426120

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

704674

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32450

American (AMR)

AF:

0.00

AC:

AN:

41140

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24182

East Asian (EAS)

AF:

0.00

AC:

AN:

39084

South Asian (SAS)

AF:

0.0000120

AC:

AN:

83074

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52018

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5584

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1090080

Other (OTH)

AF:

0.00

AC:

AN:

58508

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.078

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.34

M_CAP

Benign

0.040

MetaRNN

Benign

0.064

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

PhyloP100

0.44

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.40

REVEL

Benign

0.060

Sift

Benign

0.25

Sift4G

Uncertain

0.035

Polyphen

0.0

Vest4

0.18

MutPred

0.090

Gain of glycosylation at A7 (P = 0.0994);

MVP

0.56

MPC

0.10

ClinPred

0.15

GERP RS

1.6

PromoterAI

-0.096

Neutral

(source)

Varity_R

0.095

gMVP

0.49

Mutation Taster

=91/9

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over