chr2-178432178-G-A

Position:

chr2-178432178-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2BP4_StrongBP6_Very_StrongBP7BS1

The NM_003690.5(PRKRA):c.861C>T(p.Ser287=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00298 in 1,613,034 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 (★★). Synonymous variant affecting the same amino acid position (i.e. S287S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0092 ( 0 hom., cov: 35)

Exomes 𝑓: 0.0023 ( 0 hom. )

Consequence

PRKRA
NM_003690.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.81

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 -15 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 2-178432178-G-A is Benign according to our data. Variant chr2-178432178-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 518334.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-178432178-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-1.81 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00922 (1403/152098) while in subpopulation AFR AF= 0.0294 (1217/41368). AF 95% confidence interval is 0.028. There are 0 homozygotes in gnomad4. There are 646 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.861C>T	p.Ser287=	synonymous_variant	8/8	ENST00000325748.9
CHROMR	NR_110204.1 linkuse as main transcript	n.872-1204G>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.861C>T	p.Ser287=	synonymous_variant	8/8	1	NM_003690.5	P1	O75569-1
CHROMR	ENST00000453026.7 linkuse as main transcript	n.896-1204G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00919

AC:

1396

AN:

151978

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0293

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00511

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00125

Gnomad OTH

AF:

0.00911

GnomAD3 exomes

AF:

0.00234

AC:

587

AN:

250752

Hom.:

AF XY:

0.00189

AC XY:

256

AN XY:

135598

show subpopulations

Gnomad AFR exome

AF:

0.0226

Gnomad AMR exome

AF:

0.00256

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00111

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00233

AC:

3406

AN:

1460936

Hom.:

Cov.:

AF XY:

0.00211

AC XY:

1534

AN XY:

726770

show subpopulations

Gnomad4 AFR exome

AF:

0.0251

Gnomad4 AMR exome

AF:

0.00383

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.000162

Gnomad4 FIN exome

AF:

0.0000936

Gnomad4 NFE exome

AF:

0.00197

Gnomad4 OTH exome

AF:

0.00287

GnomAD4 genome

AF:

0.00922

AC:

1403

AN:

152098

Hom.:

Cov.:

AF XY:

0.00869

AC XY:

646

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.0294

Gnomad4 AMR

AF:

0.00510

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00125

Gnomad4 OTH

AF:

0.00901

Alfa

AF:

0.00203

Hom.:

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.000546

EpiControl

AF:

0.000949

ClinVar

Significance: Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Dystonia 16

Benign:3

Likely benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Oct 15, 2021	- -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jul 14, 2022	- -

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 19, 2021	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

5.6

DANN

Benign

0.73

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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