Variant 2-178431784-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6BA1

The NM_003690.5(PRKRA):c.*313G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 371,174 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.23 ( 0 hom., cov: 35)

Exomes 𝑓: 0.29 ( 9 hom. )

Consequence

PRKRA
NM_003690.5 3_prime_UTR

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 1.25

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 2-178431784-C-T is Benign according to our data. Variant chr2-178431784-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 332613.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1}.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.267 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.*313G>A		3_prime_UTR_variant	8/8	ENST00000325748.9
CHROMR	NR_110204.1 linkuse as main transcript	n.871+895C>T		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.*313G>A		3_prime_UTR_variant	8/8	1	NM_003690.5	P1	O75569-1
CHROMR	ENST00000453026.7 linkuse as main transcript	n.895+895C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.225

AC:

33886

AN:

150366

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.160

Gnomad AMI

AF:

0.321

Gnomad AMR

AF:

0.265

Gnomad ASJ

AF:

0.268

Gnomad EAS

AF:

0.278

Gnomad SAS

AF:

0.217

Gnomad FIN

AF:

0.203

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.253

Gnomad OTH

AF:

0.226

GnomAD4 exome

AF:

0.290

AC:

63994

AN:

220690

Hom.:

Cov.:

AF XY:

0.284

AC XY:

33113

AN XY:

116714

show subpopulations

Gnomad4 AFR exome

AF:

0.188

Gnomad4 AMR exome

AF:

0.328

Gnomad4 ASJ exome

AF:

0.328

Gnomad4 EAS exome

AF:

0.349

Gnomad4 SAS exome

AF:

0.205

Gnomad4 FIN exome

AF:

0.256

Gnomad4 NFE exome

AF:

0.304

Gnomad4 OTH exome

AF:

0.303

GnomAD4 genome

AF:

0.225

AC:

33909

AN:

150484

Hom.:

Cov.:

AF XY:

0.223

AC XY:

16406

AN XY:

73462

show subpopulations

Gnomad4 AFR

AF:

0.160

Gnomad4 AMR

AF:

0.265

Gnomad4 ASJ

AF:

0.268

Gnomad4 EAS

AF:

0.279

Gnomad4 SAS

AF:

0.216

Gnomad4 FIN

AF:

0.203

Gnomad4 NFE

AF:

0.253

Gnomad4 OTH

AF:

0.224

Alfa

AF:

0.224

Hom.:

Asia WGS

AF:

0.209

AC:

728

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Dystonia 16

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.78

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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