Variant 1-200641221-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6_ModerateBS1

The NM_001320181.2(DDX59):c.1632T>G(p.Ile544Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000422 in 1,304,780 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00091 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00036 ( 0 hom. )

Consequence

DDX59
NM_001320181.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.00

Variant links:

Genes affected

DDX59 (HGNC:25360): (DEAD-box helicase 59) Predicted to enable RNA binding activity and RNA helicase activity. Predicted to be located in cytoplasm and nucleus. Predicted to be integral component of membrane. Implicated in orofaciodigital syndrome V. [provided by Alliance of Genome Resources, Apr 2022]

DDX59 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0047310293).

BP6

Variant 1-200641221-A-C is Benign according to our data. Variant chr1-200641221-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 3058319.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000906 (138/152350) while in subpopulation EAS AF= 0.00867 (45/5190). AF 95% confidence interval is 0.00666. There are 0 homozygotes in gnomad4. There are 87 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons
DDX59	NM_001320181.2 linkuse as main transcript	c.1632T>G	p.Ile544Met	missense_variant	8/8
DDX59	XM_047431471.1 linkuse as main transcript	c.1380T>G	p.Ile460Met	missense_variant	7/7
DDX59	XM_047431472.1 linkuse as main transcript	c.1380T>G	p.Ile460Met	missense_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	UniProt
DDX59	ENST00000413408.5 linkuse as main transcript	c.546T>G	p.Ile182Met	missense_variant	4/4	5
DDX59	ENST00000447706.6 linkuse as main transcript	c.1596+7218T>G		intron_variant		2	Q5T1V6-2
DDX59	ENST00000452560.5 linkuse as main transcript	c.206-36T>G		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000907

AC:

138

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00865

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00659

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00114

AC:

173

AN:

151370

Hom.:

AF XY:

0.00107

AC XY:

AN XY:

81016

show subpopulations

Gnomad AFR exome

AF:

0.000140

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00648

Gnomad SAS exome

AF:

0.0000888

Gnomad FIN exome

AF:

0.00482

Gnomad NFE exome

AF:

0.000266

Gnomad OTH exome

AF:

0.000678

GnomAD4 exome

AF:

0.000358

AC:

412

AN:

1152430

Hom.:

Cov.:

AF XY:

0.000350

AC XY:

198

AN XY:

565080

show subpopulations

Gnomad4 AFR exome

AF:

0.0000410

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00670

Gnomad4 SAS exome

AF:

0.000184

Gnomad4 FIN exome

AF:

0.00433

Gnomad4 NFE exome

AF:

0.000164

Gnomad4 OTH exome

AF:

0.000957

GnomAD4 genome

AF:

0.000906

AC:

138

AN:

152350

Hom.:

Cov.:

AF XY:

0.00117

AC XY:

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00867

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00659

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000350

Hom.:

Bravo

AF:

0.000465

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000538

AC:

Asia WGS

AF:

0.00779

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

DDX59-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 02, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.78

CADD

Benign

9.0

DANN

Benign

0.55

Eigen

Benign

-0.97

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.072

LIST_S2

Benign

0.22

MetaRNN

Benign

0.0047

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N

PROVEAN

Benign

0.14

REVEL

Benign

0.062

Sift

Benign

0.22

Sift4G

Benign

0.074

MVP

0.085

ClinPred

0.0045

GERP RS

0.82

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over