10-68913239-C-T

Position:

chr10-68913239-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_024045.2(DDX50):c.717C>T(p.Ser239Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000912 in 1,613,242 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0048 ( 8 hom., cov: 32)

Exomes 𝑓: 0.00051 ( 4 hom. )

Consequence

DDX50
NM_024045.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.84

Variant links:

Genes affected

DDX50 (HGNC:17906): (DExD-box helicase 50) 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 DEAD box protein family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box enzyme that may be involved in ribosomal RNA synthesis or processing. This gene and DDX21, also called RH-II/GuA, have similar genomic structures and are in tandem orientation on chromosome 10, suggesting that the two genes arose by gene duplication in evolution. This gene has pseudogenes on chromosomes 2, 3 and 4. Alternative splicing of this gene generates multiple transcript variants, but the full length nature of all the other variants but one has not been defined. [provided by RefSeq, Jul 2008]

DDX50 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 10-68913239-C-T is Benign according to our data. Variant chr10-68913239-C-T is described in ClinVar as [Benign]. Clinvar id is 710605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.84 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00481 (732/152232) while in subpopulation AFR AF= 0.0166 (689/41540). AF 95% confidence interval is 0.0156. There are 8 homozygotes in gnomad4. There are 358 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX50	NM_024045.2 linkuse as main transcript	c.717C>T	p.Ser239Ser	synonymous_variant	5/15	ENST00000373585.8	NP_076950.1	Q9BQ39

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DDX50	ENST00000373585.8 linkuse as main transcript	c.717C>T	p.Ser239Ser	synonymous_variant	5/15	1	NM_024045.2	ENSP00000362687.3	Q9BQ39
DDX50	ENST00000483593.5 linkuse as main transcript	n.*651C>T		non_coding_transcript_exon_variant	6/7	3		ENSP00000474785.1	S4R3V4
DDX50	ENST00000483593.5 linkuse as main transcript	n.*651C>T		3_prime_UTR_variant	6/7	3		ENSP00000474785.1	S4R3V4
DDX50	ENST00000471475.1 linkuse as main transcript	n.*673C>T		downstream_gene_variant		5		ENSP00000474314.1	S4R3G6

Frequencies

GnomAD3 genomes

AF:

0.00482

AC:

733

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0167

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00135

AC:

338

AN:

250420

Hom.:

AF XY:

0.000902

AC XY:

122

AN XY:

135296

show subpopulations

Gnomad AFR exome

AF:

0.0179

Gnomad AMR exome

AF:

0.000932

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000881

Gnomad OTH exome

AF:

0.000981

GnomAD4 exome

AF:

0.000506

AC:

740

AN:

1461010

Hom.:

Cov.:

AF XY:

0.000449

AC XY:

326

AN XY:

726722

show subpopulations

Gnomad4 AFR exome

AF:

0.0174

Gnomad4 AMR exome

AF:

0.000988

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000450

Gnomad4 OTH exome

AF:

0.000977

GnomAD4 genome

AF:

0.00481

AC:

732

AN:

152232

Hom.:

Cov.:

AF XY:

0.00481

AC XY:

358

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0166

Gnomad4 AMR

AF:

0.00164

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.000400

Hom.:

Bravo

AF:

0.00569

EpiCase

AF:

0.000164

EpiControl

AF:

0.000296

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 04, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

1.0

DANN

Benign

0.74

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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