2-178431654-ACAAT-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_003690.5(PRKRA):c.*439_*442del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 189,578 control chromosomes in the GnomAD database, including 16 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (5 hom., cov: 21)
  • Exomes 𝑓: 0.29 (11 hom.)
• Consequence: PRKRA NM_003690.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.811

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 -10 ACMG points.

• BP6: Variant 2-178431654-ACAAT-A is Benign according to our data. Variant chr2-178431654-ACAAT-A is described in ClinVar as [Benign]. Clinvar id is 332612.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKRA	NM_003690.5	c.*439_*442del		3_prime_UTR_variant	8/8	ENST00000325748.9
CHROMR	NR_110204.1	n.871+772_871+775del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKRA	ENST00000325748.9	c.*439_*442del		3_prime_UTR_variant	8/8	1	NM_003690.5	P1
CHROMR	ENST00000453026.7	n.895+772_895+775del		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.222 AC: 32991 AN: 148488 Hom.: 4 Cov.: 21

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.205

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.223

GnomAD4 exome AF: 0.287 AC: 11744 AN: 40968 Hom.: 11 AF XY: 0.284 AC XY: 6001 AN XY: 21166

Gnomad4 AFR exome AF: 0.168

Gnomad4 AMR exome AF: 0.272

Gnomad4 ASJ exome AF: 0.321

Gnomad4 EAS exome AF: 0.285

Gnomad4 SAS exome AF: 0.245

Gnomad4 FIN exome AF: 0.239

Gnomad4 NFE exome AF: 0.303

Gnomad4 OTH exome AF: 0.299

GnomAD4 genome AF: 0.222 AC: 33017 AN: 148610 Hom.: 5 Cov.: 21 AF XY: 0.220 AC XY: 16013 AN XY: 72638

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.263

Gnomad4 ASJ AF: 0.265

Gnomad4 EAS AF: 0.275

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.250

Gnomad4 OTH AF: 0.221

Alfa AF: 0.0645 Hom.: 0

Asia WGS AF: 0.217 AC: 755 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Dystonic disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs3997880; hg19: chr2-179296381;