Variant 2-178431897-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 2P and 14B. PM2BP4_ModerateBP6_Very_StrongBS1

The NM_003690.5(PRKRA):c.*200G>A variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0202 in 665,466 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 0 hom., cov: 35)

Exomes 𝑓: 0.020 ( 0 hom. )

Consequence

PRKRA
NM_003690.5 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 4.25

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 -12 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP6

Variant 2-178431897-C-T is Benign according to our data. Variant chr2-178431897-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 894034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0195 (2954/151868) while in subpopulation NFE AF= 0.0216 (1463/67858). AF 95% confidence interval is 0.0206. There are 0 homozygotes in gnomad4. There are 1430 alleles in male gnomad4 subpopulation. Median coverage is 35. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKRA	NM_003690.5 linkuse as main transcript	c.*200G>A		3_prime_UTR_variant	8/8	ENST00000325748.9
CHROMR	NR_110204.1 linkuse as main transcript	n.871+1008C>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.*200G>A		3_prime_UTR_variant	8/8	1	NM_003690.5	P1	O75569-1
CHROMR	ENST00000453026.7 linkuse as main transcript	n.895+1008C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0195

AC:

2954

AN:

151750

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00629

Gnomad ASJ

AF:

0.0284

Gnomad EAS

AF:

0.0178

Gnomad SAS

AF:

0.0108

Gnomad FIN

AF:

0.0296

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0216

Gnomad OTH

AF:

0.0167

GnomAD4 exome

AF:

0.0204

AC:

10500

AN:

513598

Hom.:

Cov.:

AF XY:

0.0204

AC XY:

5506

AN XY:

270308

show subpopulations

Gnomad4 AFR exome

AF:

0.0197

Gnomad4 AMR exome

AF:

0.00851

Gnomad4 ASJ exome

AF:

0.0333

Gnomad4 EAS exome

AF:

0.00807

Gnomad4 SAS exome

AF:

0.0118

Gnomad4 FIN exome

AF:

0.0290

Gnomad4 NFE exome

AF:

0.0225

Gnomad4 OTH exome

AF:

0.0186

GnomAD4 genome

AF:

0.0195

AC:

2954

AN:

151868

Hom.:

Cov.:

AF XY:

0.0193

AC XY:

1430

AN XY:

74248

show subpopulations

Gnomad4 AFR

AF:

0.0193

Gnomad4 AMR

AF:

0.00622

Gnomad4 ASJ

AF:

0.0284

Gnomad4 EAS

AF:

0.0178

Gnomad4 SAS

AF:

0.0106

Gnomad4 FIN

AF:

0.0296

Gnomad4 NFE

AF:

0.0216

Gnomad4 OTH

AF:

0.0166

Alfa

AF:

0.0223

Hom.:

Asia WGS

AF:

0.0110

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Dystonia 16

Benign:1

Benign, 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 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

-0.31

CADD

Benign

DANN

Benign

0.83

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