rs2059691

Variant names:

• chr2-178437157-A-G
• rs2059691
• NM_003690.5:c.610-838T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003690.5(PRKRA):​c.610-838T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 152,048 control chromosomes in the GnomAD database, including 39,709 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.72 (39709 hom., cov: 32)
• Consequence: PRKRA NM_003690.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.298
• Publications: 13 publications found

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]

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.841 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003690.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKRA	NM_003690.5	MANE Select	c.610-838T>C		intron	N/A	NP_003681.1	O75569-1
	PRKRA	NM_001139517.1		c.577-838T>C		intron	N/A	NP_001132989.1	O75569-2
	PRKRA	NM_001139518.1		c.535-838T>C		intron	N/A	NP_001132990.1	O75569-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKRA	ENST00000325748.9	TSL:1 MANE Select	c.610-838T>C		intron	N/A	ENSP00000318176.4	O75569-1
	PRKRA	ENST00000432031.6	TSL:1	c.577-838T>C		intron	N/A	ENSP00000393883.2	O75569-2
	PRKRA	ENST00000487082.5	TSL:1	c.535-838T>C		intron	N/A	ENSP00000430604.1	O75569-3

Frequencies

GnomAD3 genomes AF: 0.720 AC: 109400 AN: 151930 Hom.: 39650 Cov.: 32

Gnomad AFR AF: 0.757

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.728

Gnomad SAS AF: 0.863

Gnomad FIN AF: 0.795

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.705

Gnomad OTH AF: 0.667

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.720 AC: 109522 AN: 152048 Hom.: 39709 Cov.: 32 AF XY: 0.725 AC XY: 53887 AN XY: 74334

African (AFR) AF: 0.757 AC: 31404 AN: 41478

American (AMR) AF: 0.632 AC: 9660 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.608 AC: 2108 AN: 3466

East Asian (EAS) AF: 0.728 AC: 3762 AN: 5170

South Asian (SAS) AF: 0.863 AC: 4161 AN: 4822

European-Finnish (FIN) AF: 0.795 AC: 8403 AN: 10576

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.705 AC: 47880 AN: 67940

Other (OTH) AF: 0.671 AC: 1416 AN: 2110

Alfa AF: 0.696 Hom.: 57451

Bravo AF: 0.700

Asia WGS AF: 0.792 AC: 2740 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.34
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2059691; hg19: chr2-179301884;