Variant chr2-178432094-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003690.5(PRKRA):c.*3C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 150,408 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 Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 0 hom., cov: 35)

Exomes 𝑓: 0.26 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

PRKRA
NM_003690.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0510

Variant links:

Genes affected

PRKRA (HGNC:9438): (protein activator of interferon induced protein kinase EIF2AK2) This gene encodes a protein kinase activated by double-stranded RNA which mediates the effects of interferon in response to viral infection. Mutations in this gene have been associated with dystonia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2008]

PRKRA links:

CHROMR (HGNC:54059): (cholesterol induced regulator of metabolism RNA)

CHROMR 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=-0.83).

BP6

Variant 2-178432094-G-A is Benign according to our data. Variant chr2-178432094-G-A is described in ClinVar as [Benign]. Clinvar id is 332620.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-178432094-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKRA	NM_003690.5 linkuse as main transcript	c.*3C>T		3_prime_UTR_variant	8/8	ENST00000325748.9
CHROMR	NR_110204.1 linkuse as main transcript	n.871+1205G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKRA	ENST00000325748.9 linkuse as main transcript	c.*3C>T		3_prime_UTR_variant	8/8	1	NM_003690.5	P1	O75569-1
CHROMR	ENST00000453026.7 linkuse as main transcript	n.895+1205G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.225

AC:

33833

AN:

150292

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.160

Gnomad AMI

AF:

0.321

Gnomad AMR

AF:

0.265

Gnomad ASJ

AF:

0.267

Gnomad EAS

AF:

0.279

Gnomad SAS

AF:

0.217

Gnomad FIN

AF:

0.203

Gnomad MID

AF:

0.212

Gnomad NFE

AF:

0.253

Gnomad OTH

AF:

0.228

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.263

AC:

378902

AN:

1440070

Hom.:

Cov.:

AF XY:

0.259

AC XY:

185824

AN XY:

716690

show subpopulations

Gnomad4 AFR exome

AF:

0.151

Gnomad4 AMR exome

AF:

0.287

Gnomad4 ASJ exome

AF:

0.264

Gnomad4 EAS exome

AF:

0.295

Gnomad4 SAS exome

AF:

0.197

Gnomad4 FIN exome

AF:

0.206

Gnomad4 NFE exome

AF:

0.273

Gnomad4 OTH exome

AF:

0.252

GnomAD4 genome

AF:

0.225

AC:

33855

AN:

150408

Hom.:

Cov.:

AF XY:

0.223

AC XY:

16375

AN XY:

73436

show subpopulations

Gnomad4 AFR

AF:

0.160

Gnomad4 AMR

AF:

0.265

Gnomad4 ASJ

AF:

0.267

Gnomad4 EAS

AF:

0.280

Gnomad4 SAS

AF:

0.217

Gnomad4 FIN

AF:

0.203

Gnomad4 NFE

AF:

0.253

Gnomad4 OTH

AF:

0.226

Alfa

AF:

0.135

Hom.:

Asia WGS

AF:

0.210

AC:

730

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

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	GeneDx	Aug 03, 2018	- -

Dystonia 16

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.0

DANN

Benign

0.60

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