2-178432255-C-CTATATCCAAATATGTTATATTAAAACCT

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_003690.5(PRKRA):c.785-2_785-1insAGGTTTTAATATAACATATTTGGATATA variant causes a splice acceptor change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 35)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRKRA NM_003690.5 splice_acceptor
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.98

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 Pathogenic. Variant got 10 ACMG points.

• PVS1: Splicing variant, LoF is a know mechanism of disease,
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKRA	NM_003690.5	c.785-2_785-1insAGGTTTTAATATAACATATTTGGATATA		splice_acceptor_variant		ENST00000325748.9
CHROMR	NR_110204.1	n.872-1126_872-1125insATATCCAAATATGTTATATTAAAACCTT		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKRA	ENST00000325748.9	c.785-2_785-1insAGGTTTTAATATAACATATTTGGATATA		splice_acceptor_variant		1	NM_003690.5	P1
CHROMR	ENST00000453026.7	n.896-1126_896-1125insATATCCAAATATGTTATATTAAAACCTT		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1461824 Hom.: 0 Cov.: 56 AF XY: 0.00 AC XY: 0 AN XY: 727220

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

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: rs751875722; hg19: chr2-179296982;