rs12984558

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_014681.6(DHX34):c.49C>T(p.Arg17Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0579 in 1,614,032 control chromosomes in the GnomAD database, including 3,216 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.046 ( 225 hom., cov: 32)

Exomes 𝑓: 0.059 ( 2991 hom. )

Consequence

DHX34
NM_014681.6 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.05

Publications

16 publications found

Variant links:

COSMIC-nc: COSV107410461

Genes affected

DHX34 (HGNC:16719): (DExH-box helicase 34) 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 member of this family. It is mapped to the glioma 19q tumor suppressor region and is a tumor suppressor candidate gene. [provided by RefSeq, Jul 2008]

DHX34 Gene-Disease associations (from GenCC):

intellectual disability
Inheritance: AR Classification: LIMITED Submitted by: G2P

DHX34 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020906627).

BP6

Variant 19-47353079-C-T is Benign according to our data. Variant chr19-47353079-C-T is described in ClinVar as [Benign]. Clinvar id is 3056984.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHX34	NM_014681.6 link	c.49C>T	p.Arg17Trp	missense_variant	Exon 2 of 17	ENST00000328771.9	NP_055496.2	Q14147

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DHX34	ENST00000328771.9 link	c.49C>T	p.Arg17Trp	missense_variant	Exon 2 of 17	5	NM_014681.6	ENSP00000331907.4	Q14147
DHX34	ENST00000718252.1 link	c.49C>T	p.Arg17Trp	missense_variant	Exon 2 of 17			ENSP00000520696.1
DHX34	ENST00000718251.1 link	n.367C>T		non_coding_transcript_exon_variant	Exon 2 of 14

Frequencies

GnomAD3 genomes

AF:

0.0459

AC:

6984

AN:

152154

Hom.:

225

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0121

Gnomad AMI

AF:

0.0614

Gnomad AMR

AF:

0.0441

Gnomad ASJ

AF:

0.0657

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0122

Gnomad FIN

AF:

0.0625

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0689

Gnomad OTH

AF:

0.0516

GnomAD2 exomes

AF:

0.0472

AC:

11860

AN:

251054

AF XY:

0.0478

show subpopulations

Gnomad AFR exome

AF:

0.00933

Gnomad AMR exome

AF:

0.0329

Gnomad ASJ exome

AF:

0.0650

Gnomad EAS exome

AF:

0.000272

Gnomad FIN exome

AF:

0.0628

Gnomad NFE exome

AF:

0.0687

Gnomad OTH exome

AF:

0.0550

GnomAD4 exome

AF:

0.0591

AC:

86413

AN:

1461760

Hom.:

2991

Cov.:

AF XY:

0.0583

AC XY:

42391

AN XY:

727164

show subpopulations

African (AFR)

AF:

0.00947

AC:

317

AN:

33478

American (AMR)

AF:

0.0334

AC:

1494

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0661

AC:

1728

AN:

26136

East Asian (EAS)

AF:

0.000151

AC:

AN:

39696

South Asian (SAS)

AF:

0.0139

AC:

1201

AN:

86256

European-Finnish (FIN)

AF:

0.0626

AC:

3342

AN:

53406

Middle Eastern (MID)

AF:

0.0470

AC:

271

AN:

5768

European-Non Finnish (NFE)

AF:

0.0673

AC:

74840

AN:

1111906

Other (OTH)

AF:

0.0532

AC:

3214

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

5297

10594

15890

21187

26484

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0459

AC:

6984

AN:

152272

Hom.:

225

Cov.:

AF XY:

0.0443

AC XY:

3296

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.0120

AC:

500

AN:

41568

American (AMR)

AF:

0.0440

AC:

673

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0657

AC:

228

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5184

South Asian (SAS)

AF:

0.0124

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0625

AC:

663

AN:

10608

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0689

AC:

4687

AN:

68006

Other (OTH)

AF:

0.0511

AC:

108

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

341

681

1022

1362

1703

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0605

Hom.:

1055

Bravo

AF:

0.0433

TwinsUK

AF:

0.0623

AC:

231

ALSPAC

AF:

0.0573

AC:

221

ESP6500AA

AF:

0.0129

AC:

ESP6500EA

AF:

0.0672

AC:

578

ExAC

AF:

0.0474

AC:

5755

Asia WGS

AF:

0.00924

AC:

AN:

3478

EpiCase

AF:

0.0695

EpiControl

AF:

0.0705

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DHX34-related disorder

Benign:1

Feb 04, 2020

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as 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

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.76

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.019

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.086

LIST_S2

Benign

0.66

MetaRNN

Benign

0.0021

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.68

PhyloP100

-1.1

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.84

REVEL

Benign

0.0080

Sift

Benign

0.14

Sift4G

Benign

0.072

Polyphen

0.0010

Vest4

0.063

MPC

0.19

ClinPred

0.0068

GERP RS

-0.37

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.037

gMVP

0.33

Mutation Taster

=98/2

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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rs12984558

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over