2-178431521-C-CACA

Variant summary

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

The NM_003690.5(PRKRA):c.*575_*576insTGT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 142,988 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.21 (0 hom., cov: 23)
  • Exomes 𝑓: 0.27 (0 hom.)
• Consequence: PRKRA NM_003690.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.744

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 2-178431521-C-CACA is Benign according to our data. Variant chr2-178431521-C-CACA is described in ClinVar as [Benign]. Clinvar id is 332611.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKRA	NM_003690.5	c.*575_*576insTGT		3_prime_UTR_variant	8/8	ENST00000325748.9
CHROMR	NR_110204.1	n.871+634_871+636dup		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKRA	ENST00000325748.9	c.*575_*576insTGT		3_prime_UTR_variant	8/8	1	NM_003690.5	P1
CHROMR	ENST00000453026.7	n.895+634_895+636dup		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.205 AC: 28740 AN: 140130 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.306

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.208

GnomAD4 exome AF: 0.265 AC: 726 AN: 2738 Hom.: 0 Cov.: 0 AF XY: 0.263 AC XY: 391 AN XY: 1488

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.290

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.350

Gnomad4 SAS exome AF: 0.197

Gnomad4 FIN exome AF: 0.172

Gnomad4 NFE exome AF: 0.279

Gnomad4 OTH exome AF: 0.308

GnomAD4 genome AF: 0.205 AC: 28764 AN: 140250 Hom.: 0 Cov.: 23 AF XY: 0.203 AC XY: 13886 AN XY: 68468

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.250

Gnomad4 EAS AF: 0.261

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.233

Gnomad4 OTH AF: 0.206

Alfa AF: 0.224 Hom.: 0

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

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs145339215; hg19: chr2-179296248;