2-178449632-G-C

Variant names:

• chr2-178449632-G-C
• rs1967327
• NM_003690.5:c.235+610C>G

Variant summary

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

The NM_003690.5(PRKRA):​c.235+610C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,122 control chromosomes in the GnomAD database, including 3,370 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 0.20 (3370 hom., cov: 33)
• Consequence: PRKRA NM_003690.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.388
• Publications: 8 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]

PRKRA Gene-Disease associations (from GenCC):

• dystonia 16

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKRA	NM_003690.5	c.235+610C>G		intron_variant	Intron 2 of 7	ENST00000325748.9	NP_003681.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKRA	ENST00000325748.9	c.235+610C>G		intron_variant	Intron 2 of 7	1	NM_003690.5	ENSP00000318176.4

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30322 AN: 152004 Hom.: 3363 Cov.: 33

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.200 AC: 30350 AN: 152122 Hom.: 3370 Cov.: 33 AF XY: 0.204 AC XY: 15142 AN XY: 74364

African (AFR) AF: 0.204 AC: 8440 AN: 41472

American (AMR) AF: 0.173 AC: 2642 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 680 AN: 3472

East Asian (EAS) AF: 0.509 AC: 2632 AN: 5176

South Asian (SAS) AF: 0.334 AC: 1611 AN: 4830

European-Finnish (FIN) AF: 0.181 AC: 1911 AN: 10570

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.172 AC: 11711 AN: 67986

Other (OTH) AF: 0.196 AC: 414 AN: 2112

Alfa AF: 0.0957 Hom.: 140

Bravo AF: 0.197

Asia WGS AF: 0.401 AC: 1393 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.0
DANN	Benign	0.43
PhyloP100		-0.39
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: rs1967327; hg19: chr2-179314359;