2-178431521-C-CACA

Variant names:

• chr2-178431521-C-CACA
• rs145339215
• NM_003690.5:c.*573_*575dupTGT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_003690.5(PRKRA):​c.*573_*575dupTGT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 142,988 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.21 (0 hom., cov: 23)
  • Exomes 𝑓: 0.27 (0 hom.)
• Consequence: PRKRA NM_003690.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.744
• 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: Variant has high frequency in the EAS (0.256) population. However there is too low homozygotes in high coverage region: (expected more than 1520, got 0).
• BP6: Variant 2-178431521-C-CACA is Benign according to our data. Variant chr2-178431521-C-CACA is described in ClinVar as Benign. ClinVar VariationId is 332611.Status of the report is criteria_provided_single_submitter, 1 stars.

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.*573_*575dupTGT		3_prime_UTR	Exon 8 of 8	NP_003681.1	O75569-1
	PRKRA	NM_001139517.1		c.*573_*575dupTGT		3_prime_UTR	Exon 7 of 7	NP_001132989.1	O75569-2
	PRKRA	NM_001139518.1		c.*573_*575dupTGT		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.*573_*575dupTGT		3_prime_UTR	Exon 8 of 8	ENSP00000318176.4	O75569-1
	PRKRA	ENST00000914393.1		c.*573_*575dupTGT		3_prime_UTR	Exon 8 of 8	ENSP00000584452.1
	PRKRA	ENST00000677981.1		c.*573_*575dupTGT		3_prime_UTR	Exon 6 of 6	ENSP00000503536.1	A0A7I2V3J2

Frequencies

GnomAD3 genomes AF: 0.205 AC: 28740 AN: 140130 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.306

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.208

GnomAD4 exome AF: 0.265 AC: 726 AN: 2738 Hom.: 0 Cov.: 0 AF XY: 0.263 AC XY: 391 AN XY: 1488

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

African (AFR) AF: 0.00 AC: 0 AN: 6

American (AMR) AF: 0.290 AC: 182 AN: 628

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 6 AN: 12

East Asian (EAS) AF: 0.350 AC: 21 AN: 60

South Asian (SAS) AF: 0.197 AC: 41 AN: 208

European-Finnish (FIN) AF: 0.172 AC: 56 AN: 326

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.279 AC: 396 AN: 1420

Other (OTH) AF: 0.308 AC: 24 AN: 78

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.205 AC: 28764 AN: 140250 Hom.: 0 Cov.: 23 AF XY: 0.203 AC XY: 13886 AN XY: 68468

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

African (AFR) AF: 0.141 AC: 5490 AN: 38946

American (AMR) AF: 0.246 AC: 3417 AN: 13916

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 798 AN: 3188

East Asian (EAS) AF: 0.261 AC: 1231 AN: 4722

South Asian (SAS) AF: 0.194 AC: 850 AN: 4390

European-Finnish (FIN) AF: 0.181 AC: 1765 AN: 9726

Middle Eastern (MID) AF: 0.182 AC: 50 AN: 274

European-Non Finnish (NFE) AF: 0.233 AC: 14505 AN: 62300

Other (OTH) AF: 0.206 AC: 405 AN: 1962

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.224 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Dystonic disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.74
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs145339215; hg19: chr2-179296248; COSMIC: COSV57867509; COSMIC: COSV57867509;