Variant chr20-49241753-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_017895.8(DDX27):c.1898-140G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 879,170 control chromosomes in the GnomAD database, including 17,476 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.19 ( 2810 hom., cov: 32)

Exomes 𝑓: 0.19 ( 14666 hom. )

Consequence

DDX27
NM_017895.8 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.531

Variant links:

Genes affected

DDX27 (HGNC:15837): (DEAD-box helicase 27) 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 involved in the processing of 5.8S and 28S ribosomal RNAs. More specifically, the encoded protein localizes to the nucleolus, where it interacts with the PeBoW complex to ensure proper 3' end formation of 47S rRNA. [provided by RefSeq, Jan 2017]

DDX27 links:

ZNFX1 (HGNC:29271): (zinc finger NFX1-type containing 1) Enables RNA binding activity. Predicted to be involved in heterochromatin assembly by small RNA. Predicted to be part of nuclear RNA-directed RNA polymerase complex. [provided by Alliance of Genome Resources, Apr 2022]

ZNFX1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 20-49241753-G-A is Benign according to our data. Variant chr20-49241753-G-A is described in ClinVar as [Benign]. Clinvar id is 2688265.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDX27	NM_017895.8 linkuse as main transcript	c.1898-140G>A		intron_variant		ENST00000618172.5
DDX27	NM_001348187.2 linkuse as main transcript	c.1991-140G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDX27	ENST00000618172.5 linkuse as main transcript	c.1898-140G>A		intron_variant		1	NM_017895.8	P1

Frequencies

GnomAD3 genomes

AF:

0.190

AC:

28876

AN:

151840

Hom.:

2809

Cov.:

show subpopulations

Gnomad AFR

AF:

0.182

Gnomad AMI

AF:

0.304

Gnomad AMR

AF:

0.158

Gnomad ASJ

AF:

0.165

Gnomad EAS

AF:

0.0517

Gnomad SAS

AF:

0.0866

Gnomad FIN

AF:

0.216

Gnomad MID

AF:

0.128

Gnomad NFE

AF:

0.217

Gnomad OTH

AF:

0.156

GnomAD4 exome

AF:

0.194

AC:

141437

AN:

727212

Hom.:

14666

AF XY:

0.189

AC XY:

71497

AN XY:

377572

show subpopulations

Gnomad4 AFR exome

AF:

0.179

Gnomad4 AMR exome

AF:

0.161

Gnomad4 ASJ exome

AF:

0.170

Gnomad4 EAS exome

AF:

0.0707

Gnomad4 SAS exome

AF:

0.0856

Gnomad4 FIN exome

AF:

0.210

Gnomad4 NFE exome

AF:

0.219

Gnomad4 OTH exome

AF:

0.183

GnomAD4 genome

AF:

0.190

AC:

28893

AN:

151958

Hom.:

2810

Cov.:

AF XY:

0.185

AC XY:

13744

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.182

Gnomad4 AMR

AF:

0.158

Gnomad4 ASJ

AF:

0.165

Gnomad4 EAS

AF:

0.0516

Gnomad4 SAS

AF:

0.0879

Gnomad4 FIN

AF:

0.216

Gnomad4 NFE

AF:

0.217

Gnomad4 OTH

AF:

0.157

Alfa

AF:

0.113

Hom.:

209

Bravo

AF:

0.183

Asia WGS

AF:

0.0920

AC:

321

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 28% of patients studied by a panel of primary immunodeficiencies. Number of patients: 27. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

2.1

DANN

Benign

0.35

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

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