Variant 1-200648579-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001031725.6(DDX59):c.1468-12T>G variant causes a intron change. The variant allele was found at a frequency of 0.00281 in 1,601,580 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0018 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0029 ( 10 hom. )

Consequence

DDX59
NM_001031725.6 intron

Scores

Splicing: ADA: 0.2637

Clinical Significance

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

Conservation

PhyloP100: 4.97

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 1-200648579-A-C is Benign according to our data. Variant chr1-200648579-A-C is described in ClinVar as [Benign]. Clinvar id is 1615789.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00183 (279/152346) while in subpopulation NFE AF= 0.00323 (220/68024). AF 95% confidence interval is 0.00288. There are 1 homozygotes in gnomad4. There are 118 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX59	NM_001031725.6 linkuse as main transcript	c.1468-12T>G		intron_variant		ENST00000331314.11	NP_001026895.2	Q5T1V6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX59	ENST00000331314.11 linkuse as main transcript	c.1468-12T>G		intron_variant		1	NM_001031725.6	ENSP00000330460.6		Q5T1V6-1

Frequencies

GnomAD3 genomes

AF:

0.00183

AC:

279

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000917

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00323

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00149

AC:

358

AN:

240780

Hom.:

AF XY:

0.00140

AC XY:

183

AN XY:

130324

show subpopulations

Gnomad AFR exome

AF:

0.000436

Gnomad AMR exome

AF:

0.000611

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000426

Gnomad NFE exome

AF:

0.00280

Gnomad OTH exome

AF:

0.00224

GnomAD4 exome

AF:

0.00291

AC:

4215

AN:

1449234

Hom.:

Cov.:

AF XY:

0.00279

AC XY:

2012

AN XY:

720440

show subpopulations

Gnomad4 AFR exome

AF:

0.000396

Gnomad4 AMR exome

AF:

0.000630

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000530

Gnomad4 NFE exome

AF:

0.00360

Gnomad4 OTH exome

AF:

0.00261

GnomAD4 genome

AF:

0.00183

AC:

279

AN:

152346

Hom.:

Cov.:

AF XY:

0.00158

AC XY:

118

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.000914

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.00323

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000936

Hom.:

Bravo

AF:

0.00168

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Oct 03, 2023	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.26

dbscSNV1_RF

Benign

0.66

SpliceAI score (max)

0.090

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

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