Variant 16-70356244-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018332.5(DDX19A):c.290G>A(p.Arg97Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000279 in 1,614,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

DDX19A
NM_018332.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.90

Variant links:

Genes affected

DDX19A (HGNC:25628): (DEAD-box helicase 19A) Predicted to enable RNA binding activity and RNA helicase activity. Predicted to be involved in poly(A)+ mRNA export from nucleus. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

DDX19A links:

ENSG00000260537 (HGNC:):

ENSG00000260537 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18772358).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX19A	NM_018332.5 linkuse as main transcript	c.290G>A	p.Arg97Gln	missense_variant	4/12	ENST00000302243.12	NP_060802.1	Q9NUU7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX19A	ENST00000302243.12 linkuse as main transcript	c.290G>A	p.Arg97Gln	missense_variant	4/12	1	NM_018332.5	ENSP00000306117.7		Q9NUU7-1
ENSG00000260537	ENST00000443119.7 linkuse as main transcript	c.293G>A	p.Arg98Gln	missense_variant	4/12	5		ENSP00000399208.3		F6QDS0

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000318

AC:

AN:

251442

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000280

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000297

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152122

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000752

Hom.:

Bravo

AF:

0.0000151

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 17, 2022

The c.290G>A (p.R97Q) alteration is located in exon 4 (coding exon 4) of the DDX19A gene. This alteration results from a G to A substitution at nucleotide position 290, causing the arginine (R) at amino acid position 97 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.050

.;T;.

Eigen

Benign

-0.055

Eigen_PC

Benign

0.060

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Pathogenic

0.98

D;D;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.19

T;T;T

MetaSVM

Benign

-0.75

MutationAssessor

Benign

1.6

.;L;.

PROVEAN

Benign

-0.92

.;N;N

REVEL

Benign

0.12

Sift

Benign

0.21

.;T;T

Sift4G

Benign

0.35

T;T;T

Polyphen

0.81

.;P;.

Vest4

0.48

MutPred

0.41

.;Gain of methylation at K99 (P = 0.0564);Gain of methylation at K99 (P = 0.0564);

MVP

0.62

MPC

0.67

ClinPred

0.29

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.059

gMVP

0.36

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