chr2-178431938-A-G

Variant names:

• chr2-178431938-A-G
• rs115244185
• NM_003690.5:c.*159T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_003690.5(PRKRA):​c.*159T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0024 in 894,838 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0097 (17 hom., cov: 35)
  • Exomes 𝑓: 0.00092 (6 hom.)
• Consequence: PRKRA NM_003690.5 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0240
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 2-178431938-A-G is Benign according to our data. Variant chr2-178431938-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 332617.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00965 (1470/152324) while in subpopulation AFR AF = 0.0337 (1398/41534). AF 95% confidence interval is 0.0322. There are 17 homozygotes in GnomAd4. There are 704 alleles in the male GnomAd4 subpopulation. Median coverage is 35. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 17 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.*159T>C		3_prime_UTR	Exon 8 of 8	NP_003681.1	O75569-1
	PRKRA	NM_001139517.1		c.*159T>C		3_prime_UTR	Exon 7 of 7	NP_001132989.1	O75569-2
	PRKRA	NM_001139518.1		c.*159T>C		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.*159T>C		3_prime_UTR	Exon 8 of 8	ENSP00000318176.4	O75569-1
	PRKRA	ENST00000914393.1		c.*159T>C		3_prime_UTR	Exon 8 of 8	ENSP00000584452.1
	PRKRA	ENST00000677981.1		c.*159T>C		3_prime_UTR	Exon 6 of 6	ENSP00000503536.1	A0A7I2V3J2

Frequencies

GnomAD3 genomes AF: 0.00962 AC: 1464 AN: 152206 Hom.: 17 Cov.: 35

Gnomad AFR AF: 0.0336

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00860

GnomAD4 exome AF: 0.000919 AC: 682 AN: 742514 Hom.: 6 Cov.: 10 AF XY: 0.000824 AC XY: 315 AN XY: 382396

African (AFR) AF: 0.0316 AC: 526 AN: 16638

American (AMR) AF: 0.00198 AC: 56 AN: 28294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18168

East Asian (EAS) AF: 0.00 AC: 0 AN: 32552

South Asian (SAS) AF: 0.000179 AC: 10 AN: 55996

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35200

Middle Eastern (MID) AF: 0.00152 AC: 4 AN: 2630

European-Non Finnish (NFE) AF: 0.0000193 AC: 10 AN: 517306

Other (OTH) AF: 0.00213 AC: 76 AN: 35730

GnomAD4 genome AF: 0.00965 AC: 1470 AN: 152324 Hom.: 17 Cov.: 35 AF XY: 0.00945 AC XY: 704 AN XY: 74490

African (AFR) AF: 0.0337 AC: 1398 AN: 41534

American (AMR) AF: 0.00327 AC: 50 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5194

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68038

Other (OTH) AF: 0.00851 AC: 18 AN: 2116

Alfa AF: 0.00473 Hom.: 1

Bravo AF: 0.0110

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Dystonia 16 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	3.4
DANN	Benign	0.80
PhyloP100		-0.024
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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: rs115244185; hg19: chr2-179296665;