rs886055202

Variant names:

• chr2-178431917-G-A
• rs886055202
• NM_003690.5:c.*180C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003690.5(PRKRA):​c.*180C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 35)
• Consequence: PRKRA NM_003690.5 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.45
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).

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.*180C>T		3_prime_UTR	Exon 8 of 8	NP_003681.1	O75569-1
	PRKRA	NM_001139517.1		c.*180C>T		3_prime_UTR	Exon 7 of 7	NP_001132989.1	O75569-2
	PRKRA	NM_001139518.1		c.*180C>T		3_prime_UTR	Exon 8 of 8	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.*180C>T		3_prime_UTR	Exon 8 of 8	ENSP00000318176.4	O75569-1
	PRKRA	ENST00000914393.1		c.*180C>T		3_prime_UTR	Exon 8 of 8	ENSP00000584452.1
	PRKRA	ENST00000677981.1		c.*180C>T		3_prime_UTR	Exon 6 of 6	ENSP00000503536.1	A0A7I2V3J2

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Cov.: 8

GnomAD4 genome Cov.: 35

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Dystonia 16 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	15
DANN	Benign	0.75
PhyloP100		2.4

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

Other links and lift over

dbSNP: rs886055202; hg19: chr2-179296644;