rs188208530

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_003690.5(PRKRA):c.784+6A>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00515 in 796,824 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0030 ( 0 hom., cov: 22)

Exomes 𝑓: 0.0054 ( 12 hom. )

Consequence

PRKRA
NM_003690.5 splice_region, intron

Scores

Splicing: ADA: 0.0001641

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.0420

Publications

2 publications found

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 was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 2-178436139-T-A is Benign according to our data. Variant chr2-178436139-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 425237.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKRA	NM_003690.5 link	c.784+6A>T		splice_region_variant, intron_variant	Intron 7 of 7	ENST00000325748.9	NP_003681.1	O75569-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKRA	ENST00000325748.9 link	c.784+6A>T		splice_region_variant, intron_variant	Intron 7 of 7	1	NM_003690.5	ENSP00000318176.4		O75569-1

Frequencies

GnomAD3 genomes

AF:

0.00299

AC:

248

AN:

83058

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000537

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00197

Gnomad ASJ

AF:

0.00125

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000802

Gnomad MID

AF:

0.00549

Gnomad NFE

AF:

0.00617

Gnomad OTH

AF:

0.00353

GnomAD2 exomes

AF:

0.00263

AC:

452

AN:

172034

AF XY:

0.00255

show subpopulations

Gnomad AFR exome

AF:

0.000639

Gnomad AMR exome

AF:

0.00201

Gnomad ASJ exome

AF:

0.000683

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00150

Gnomad NFE exome

AF:

0.00462

Gnomad OTH exome

AF:

0.00270

GnomAD4 exome

AF:

0.00540

AC:

3852

AN:

713694

Hom.:

Cov.:

AF XY:

0.00516

AC XY:

1866

AN XY:

361606

show subpopulations

African (AFR)

AF:

0.000384

AC:

AN:

23416

American (AMR)

AF:

0.00307

AC:

AN:

20182

Ashkenazi Jewish (ASJ)

AF:

0.000983

AC:

AN:

13224

East Asian (EAS)

AF:

0.00

AC:

AN:

18996

South Asian (SAS)

AF:

0.000861

AC:

AN:

53452

European-Finnish (FIN)

AF:

0.00141

AC:

AN:

32606

Middle Eastern (MID)

AF:

0.00250

AC:

AN:

3200

European-Non Finnish (NFE)

AF:

0.00692

AC:

3580

AN:

517314

Other (OTH)

AF:

0.00281

AC:

AN:

31304

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

176

351

527

702

878

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

138

276

414

552

690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00298

AC:

248

AN:

83130

Hom.:

Cov.:

AF XY:

0.00252

AC XY:

103

AN XY:

40872

show subpopulations

African (AFR)

AF:

0.000536

AC:

AN:

28002

American (AMR)

AF:

0.00197

AC:

AN:

7106

Ashkenazi Jewish (ASJ)

AF:

0.00125

AC:

AN:

1598

East Asian (EAS)

AF:

0.00

AC:

AN:

2276

South Asian (SAS)

AF:

0.00

AC:

AN:

2698

European-Finnish (FIN)

AF:

0.000802

AC:

AN:

6236

Middle Eastern (MID)

AF:

0.00575

AC:

AN:

174

European-Non Finnish (NFE)

AF:

0.00617

AC:

207

AN:

33566

Other (OTH)

AF:

0.00347

AC:

AN:

1152

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00213

Hom.:

Bravo

AF:

0.00197

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Aug 04, 2021

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PRKRA: BP4, BS2 -

Dystonia 16

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Dec 16, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Benign

0.86

PhyloP100

0.042

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00016

dbscSNV1_RF

Benign

0.014

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over