1-200666422-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001031725.6(DDX59):c.319A>G(p.Ile107Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0849 in 1,614,044 control chromosomes in the GnomAD database, including 10,390 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1549 hom., cov: 32)

Exomes 𝑓: 0.081 ( 8841 hom. )

Consequence

DDX59
NM_001031725.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.75

Publications

22 publications found

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 Gene-Disease associations (from GenCC):

orofaciodigital syndrome V
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet

DDX59 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0046088994).

BP6

Variant 1-200666422-T-C is Benign according to our data. Variant chr1-200666422-T-C is described in ClinVar as Benign. ClinVar VariationId is 1530753.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031725.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DDX59	NM_001031725.6	MANE Select	c.319A>G	p.Ile107Val	missense	Exon 2 of 8	NP_001026895.2
DDX59	NM_001349799.3		c.319A>G	p.Ile107Val	missense	Exon 2 of 8	NP_001336728.1
DDX59	NM_001349800.3		c.319A>G	p.Ile107Val	missense	Exon 2 of 8	NP_001336729.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DDX59	ENST00000331314.11	TSL:1 MANE Select	c.319A>G	p.Ile107Val	missense	Exon 2 of 8	ENSP00000330460.6
DDX59	ENST00000447706.6	TSL:2	c.319A>G	p.Ile107Val	missense	Exon 2 of 8	ENSP00000394367.2
DDX59	ENST00000436897.1	TSL:3	c.319A>G	p.Ile107Val	missense	Exon 2 of 2	ENSP00000391312.1

Frequencies

GnomAD3 genomes

AF:

0.118

AC:

17996

AN:

152060

Hom.:

1547

Cov.:

show subpopulations

Gnomad AFR

AF:

0.151

Gnomad AMI

AF:

0.136

Gnomad AMR

AF:

0.195

Gnomad ASJ

AF:

0.108

Gnomad EAS

AF:

0.414

Gnomad SAS

AF:

0.177

Gnomad FIN

AF:

0.129

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0535

Gnomad OTH

AF:

0.120

GnomAD2 exomes

AF:

0.136

AC:

34204

AN:

251350

AF XY:

0.129

show subpopulations

Gnomad AFR exome

AF:

0.148

Gnomad AMR exome

AF:

0.252

Gnomad ASJ exome

AF:

0.118

Gnomad EAS exome

AF:

0.409

Gnomad FIN exome

AF:

0.122

Gnomad NFE exome

AF:

0.0550

Gnomad OTH exome

AF:

0.112

GnomAD4 exome

AF:

0.0815

AC:

119085

AN:

1461866

Hom.:

8841

Cov.:

AF XY:

0.0828

AC XY:

60209

AN XY:

727232

show subpopulations

African (AFR)

AF:

0.150

AC:

5030

AN:

33478

American (AMR)

AF:

0.247

AC:

11053

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.117

AC:

3047

AN:

26136

East Asian (EAS)

AF:

0.401

AC:

15903

AN:

39696

South Asian (SAS)

AF:

0.160

AC:

13761

AN:

86258

European-Finnish (FIN)

AF:

0.120

AC:

6407

AN:

53420

Middle Eastern (MID)

AF:

0.114

AC:

655

AN:

5768

European-Non Finnish (NFE)

AF:

0.0515

AC:

57245

AN:

1112006

Other (OTH)

AF:

0.0991

AC:

5984

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

7113

14226

21339

28452

35565

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2616

5232

7848

10464

13080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.118

AC:

18020

AN:

152178

Hom.:

1549

Cov.:

AF XY:

0.126

AC XY:

9386

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.151

AC:

6269

AN:

41512

American (AMR)

AF:

0.195

AC:

2987

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.108

AC:

373

AN:

3466

East Asian (EAS)

AF:

0.413

AC:

2129

AN:

5158

South Asian (SAS)

AF:

0.177

AC:

851

AN:

4816

European-Finnish (FIN)

AF:

0.129

AC:

1366

AN:

10602

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0534

AC:

3635

AN:

68022

Other (OTH)

AF:

0.121

AC:

256

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

800

1600

2401

3201

4001

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

192

384

576

768

960

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0782

Hom.:

1953

Bravo

AF:

0.125

TwinsUK

AF:

0.0591

AC:

219

ALSPAC

AF:

0.0542

AC:

209

ESP6500AA

AF:

0.145

AC:

639

ESP6500EA

AF:

0.0622

AC:

535

ExAC

AF:

0.129

AC:

15688

Asia WGS

AF:

0.275

AC:

954

AN:

3478

EpiCase

AF:

0.0565

EpiControl

AF:

0.0557

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.047

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.69

CADD

Benign

3.4

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.0033

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.46

MetaRNN

Benign

0.0046

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-1.8

PhyloP100

2.8

PrimateAI

Uncertain

0.61

PROVEAN

Benign

0.62

REVEL

Benign

0.11

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.017

MPC

0.14

ClinPred

0.0014

GERP RS

4.3

Varity_R

0.056

gMVP

0.089

Mutation Taster

=100/0

polymorphism (auto)

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over