rs2059691

Positions:

• chr2-178437157-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKRA	NM_003690.5	c.610-838T>C		intron_variant		ENST00000325748.9	NP_003681.1
CHROMR	NR_110204.1	n.966-1710A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKRA	ENST00000325748.9	c.610-838T>C		intron_variant		1	NM_003690.5	ENSP00000318176	P1
CHROMR	ENST00000453026.7	n.990-1710A>G		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.757

Gnomad4 AMR AF: 0.632

Gnomad4 ASJ AF: 0.608

Gnomad4 EAS AF: 0.728

Gnomad4 SAS AF: 0.863

Gnomad4 FIN AF: 0.795

Gnomad4 NFE AF: 0.705

Gnomad4 OTH AF: 0.671

Alfa AF: 0.696 Hom.: 48756

Bravo AF: 0.700

Asia WGS AF: 0.792 AC: 2740 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.34

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

Other links and lift over

dbSNP: rs2059691; hg19: chr2-179301884;