chr2-178432244-G-A

Variant names:

• chr2-178432244-G-A
• rs150679361
• NM_003690.5:c.795C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_003690.5(PRKRA):​c.795C>T​(p.Ser265Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00953 in 1,613,398 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0069 (6 hom., cov: 35)
  • Exomes 𝑓: 0.0098 (52 hom.)
• Consequence: PRKRA NM_003690.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.128
• Publications: 3 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 2-178432244-G-A is Benign according to our data. Variant chr2-178432244-G-A is described in ClinVar as Benign. ClinVar VariationId is 469612.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.128 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 6 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.795C>T	p.Ser265Ser	synonymous	Exon 8 of 8	NP_003681.1
	PRKRA	NM_001139517.1		c.762C>T	p.Ser254Ser	synonymous	Exon 7 of 7	NP_001132989.1
	PRKRA	NM_001139518.1		c.720C>T	p.Ser240Ser	synonymous	Exon 8 of 8	NP_001132990.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKRA	ENST00000325748.9	TSL:1 MANE Select	c.795C>T	p.Ser265Ser	synonymous	Exon 8 of 8	ENSP00000318176.4
	PRKRA	ENST00000432031.6	TSL:1	c.762C>T	p.Ser254Ser	synonymous	Exon 7 of 7	ENSP00000393883.2
	PRKRA	ENST00000487082.5	TSL:1	c.720C>T	p.Ser240Ser	synonymous	Exon 8 of 8	ENSP00000430604.1

Frequencies

GnomAD3 genomes AF: 0.00686 AC: 1044 AN: 152222 Hom.: 6 Cov.: 35

Gnomad AFR AF: 0.00191

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00399

Gnomad ASJ AF: 0.0202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00642

Gnomad FIN AF: 0.00584

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0106

Gnomad OTH AF: 0.0101

GnomAD2 exomes AF: 0.00777 AC: 1950 AN: 250906 AF XY: 0.00782

Gnomad AFR exome AF: 0.00154

Gnomad AMR exome AF: 0.00408

Gnomad ASJ exome AF: 0.0148

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00559

Gnomad NFE exome AF: 0.0113

Gnomad OTH exome AF: 0.0103

GnomAD4 exome AF: 0.00980 AC: 14325 AN: 1461058 Hom.: 52 Cov.: 58 AF XY: 0.00966 AC XY: 7019 AN XY: 726872

African (AFR) AF: 0.00125 AC: 42 AN: 33478

American (AMR) AF: 0.00432 AC: 193 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0145 AC: 378 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39694

South Asian (SAS) AF: 0.00599 AC: 517 AN: 86250

European-Finnish (FIN) AF: 0.00648 AC: 346 AN: 53410

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5768

European-Non Finnish (NFE) AF: 0.0111 AC: 12292 AN: 1111234

Other (OTH) AF: 0.00908 AC: 548 AN: 60370

GnomAD4 genome AF: 0.00685 AC: 1044 AN: 152340 Hom.: 6 Cov.: 35 AF XY: 0.00642 AC XY: 478 AN XY: 74496

African (AFR) AF: 0.00190 AC: 79 AN: 41582

American (AMR) AF: 0.00398 AC: 61 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0202 AC: 70 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00642 AC: 31 AN: 4826

European-Finnish (FIN) AF: 0.00584 AC: 62 AN: 10614

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

European-Non Finnish (NFE) AF: 0.0106 AC: 719 AN: 68030

Other (OTH) AF: 0.00996 AC: 21 AN: 2108

Alfa AF: 0.00852 Hom.: 1

Bravo AF: 0.00672

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.0108

EpiControl AF: 0.0103

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Dystonia 16 (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	11
DANN	Benign	0.88
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs150679361; hg19: chr2-179296971;