rs188208530

Variant names:

• chr2-178436139-T-A
• rs188208530
• NM_003690.5:c.784+6A>T

Your query was ambiguous. Multiple possible variants found:

• chr2-178436139-T-A
• chr2-178436139-T-G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_003690.5(PRKRA):​c.784+6A>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00515 in 796,824 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0030 (0 hom., cov: 22)
  • Exomes 𝑓: 0.0054 (12 hom.)
• Consequence: PRKRA NM_003690.5 splice_region, intron
• Scores: Splicing: ADA: 0.0001641
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.0420
• Publications: 2 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 2-178436139-T-A is Benign according to our data. Variant chr2-178436139-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 425237.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 12 AR gene

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.784+6A>T		splice_region intron	N/A	NP_003681.1	O75569-1
	PRKRA	NM_001139517.1		c.751+6A>T		splice_region intron	N/A	NP_001132989.1	O75569-2
	PRKRA	NM_001139518.1		c.709+6A>T		splice_region 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.784+6A>T		splice_region intron	N/A	ENSP00000318176.4	O75569-1
	PRKRA	ENST00000432031.6	TSL:1	c.751+6A>T		splice_region intron	N/A	ENSP00000393883.2	O75569-2
	PRKRA	ENST00000487082.5	TSL:1	c.709+6A>T		splice_region intron	N/A	ENSP00000430604.1	O75569-3

Frequencies

GnomAD3 genomes AF: 0.00299 AC: 248 AN: 83058 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.000537

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00197

Gnomad ASJ AF: 0.00125

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000802

Gnomad MID AF: 0.00549

Gnomad NFE AF: 0.00617

Gnomad OTH AF: 0.00353

GnomAD2 exomes AF: 0.00263 AC: 452 AN: 172034 AF XY: 0.00255

Gnomad AFR exome AF: 0.000639

Gnomad AMR exome AF: 0.00201

Gnomad ASJ exome AF: 0.000683

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00150

Gnomad NFE exome AF: 0.00462

Gnomad OTH exome AF: 0.00270

GnomAD4 exome AF: 0.00540 AC: 3852 AN: 713694 Hom.: 12 Cov.: 29 AF XY: 0.00516 AC XY: 1866 AN XY: 361606

African (AFR) AF: 0.000384 AC: 9 AN: 23416

American (AMR) AF: 0.00307 AC: 62 AN: 20182

Ashkenazi Jewish (ASJ) AF: 0.000983 AC: 13 AN: 13224

East Asian (EAS) AF: 0.00 AC: 0 AN: 18996

South Asian (SAS) AF: 0.000861 AC: 46 AN: 53452

European-Finnish (FIN) AF: 0.00141 AC: 46 AN: 32606

Middle Eastern (MID) AF: 0.00250 AC: 8 AN: 3200

European-Non Finnish (NFE) AF: 0.00692 AC: 3580 AN: 517314

Other (OTH) AF: 0.00281 AC: 88 AN: 31304

GnomAD4 genome AF: 0.00298 AC: 248 AN: 83130 Hom.: 0 Cov.: 22 AF XY: 0.00252 AC XY: 103 AN XY: 40872

African (AFR) AF: 0.000536 AC: 15 AN: 28002

American (AMR) AF: 0.00197 AC: 14 AN: 7106

Ashkenazi Jewish (ASJ) AF: 0.00125 AC: 2 AN: 1598

East Asian (EAS) AF: 0.00 AC: 0 AN: 2276

South Asian (SAS) AF: 0.00 AC: 0 AN: 2698

European-Finnish (FIN) AF: 0.000802 AC: 5 AN: 6236

Middle Eastern (MID) AF: 0.00575 AC: 1 AN: 174

European-Non Finnish (NFE) AF: 0.00617 AC: 207 AN: 33566

Other (OTH) AF: 0.00347 AC: 4 AN: 1152

Alfa AF: 0.00213 Hom.: 0

Bravo AF: 0.00197

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Dystonia 16 (2)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	15
DANN	Benign	0.86
PhyloP100		0.042
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00016
dbscSNV1_RF	Benign	0.014
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: rs188208530; hg19: chr2-179300866;