rs751875722

Variant names:

• chr2-178432255-C-CTATATCCAAATA
• rs751875722
• NM_003690.5:c.785-2_785-1insTATTTGGATATA

Your query was ambiguous. Multiple possible variants found:

• chr2-178432255-C-CTATATCCAAATA
• chr2-178432255-C-CTATATCCAAATATGTTATATTAAAACCT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_003690.5(PRKRA):​c.785-2_785-1insTATTTGGATATA variant causes a splice acceptor, intron change. The variant allele was found at a frequency of 0.00174 in 152,160 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0017 (0 hom., cov: 35)
  • Exomes 𝑓: 0.0072 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRKRA NM_003690.5 splice_acceptor, intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.98
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKRA	NM_003690.5	c.785-2_785-1insTATTTGGATATA		splice_acceptor_variant, intron_variant	Intron 7 of 7	ENST00000325748.9	NP_003681.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKRA	ENST00000325748.9	c.785-2_785-1insTATTTGGATATA		splice_acceptor_variant, intron_variant	Intron 7 of 7	1	NM_003690.5	ENSP00000318176.4

Frequencies

GnomAD3 genomes AF: 0.00174 AC: 264 AN: 152042 Hom.: 0 Cov.: 35

Gnomad AFR AF: 0.00145

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00256

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.000831

Gnomad FIN AF: 0.00245

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00156

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00249 AC: 617 AN: 247460 AF XY: 0.00253

Gnomad AFR exome AF: 0.00143

Gnomad AMR exome AF: 0.00128

Gnomad ASJ exome AF: 0.000905

Gnomad EAS exome AF: 0.00148

Gnomad FIN exome AF: 0.00489

Gnomad NFE exome AF: 0.00327

Gnomad OTH exome AF: 0.00148

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00718 AC: 10430 AN: 1453216 Hom.: 0 Cov.: 56 AF XY: 0.00685 AC XY: 4955 AN XY: 723014

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00390 AC: 130 AN: 33370

American (AMR) AF: 0.00694 AC: 308 AN: 44382

Ashkenazi Jewish (ASJ) AF: 0.00432 AC: 112 AN: 25930

East Asian (EAS) AF: 0.00242 AC: 96 AN: 39656

South Asian (SAS) AF: 0.00332 AC: 285 AN: 85798

European-Finnish (FIN) AF: 0.00304 AC: 162 AN: 53286

Middle Eastern (MID) AF: 0.00296 AC: 17 AN: 5752

European-Non Finnish (NFE) AF: 0.00813 AC: 8985 AN: 1104922

Other (OTH) AF: 0.00557 AC: 335 AN: 60120

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00174 AC: 264 AN: 152160 Hom.: 0 Cov.: 35 AF XY: 0.00164 AC XY: 122 AN XY: 74384

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00144 AC: 60 AN: 41550

American (AMR) AF: 0.00255 AC: 39 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3468

East Asian (EAS) AF: 0.00309 AC: 16 AN: 5182

South Asian (SAS) AF: 0.000831 AC: 4 AN: 4812

European-Finnish (FIN) AF: 0.00245 AC: 26 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00156 AC: 106 AN: 67968

Other (OTH) AF: 0.00237 AC: 5 AN: 2110

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00480 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Dystonia 16 Uncertain:1

Mar 18, 2016

Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: reference population

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.0
Mutation Taster		=79/21	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs751875722; hg19: chr2-179296982;