2-178431897-C-A

Variant names:

• chr2-178431897-C-A
• rs141995027
• NM_003690.5:c.*200G>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.*200G>T variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.00000194 in 516,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 35)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: PRKRA NM_003690.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.25
• 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=-0.3).

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.*200G>T		3_prime_UTR	Exon 8 of 8	NP_003681.1	O75569-1
	PRKRA	NM_001139517.1		c.*200G>T		3_prime_UTR	Exon 7 of 7	NP_001132989.1	O75569-2
	PRKRA	NM_001139518.1		c.*200G>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.*200G>T		3_prime_UTR	Exon 8 of 8	ENSP00000318176.4	O75569-1
	PRKRA	ENST00000914393.1		c.*200G>T		3_prime_UTR	Exon 8 of 8	ENSP00000584452.1
	PRKRA	ENST00000677981.1		c.*200G>T		3_prime_UTR	Exon 6 of 6	ENSP00000503536.1	A0A7I2V3J2

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome AF: 0.00000194 AC: 1 AN: 516688 Hom.: 0 Cov.: 6 AF XY: 0.00 AC XY: 0 AN XY: 271894

⚠️ 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: 13096

American (AMR) AF: 0.00 AC: 0 AN: 22514

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14398

East Asian (EAS) AF: 0.00 AC: 0 AN: 30474

South Asian (SAS) AF: 0.00 AC: 0 AN: 47528

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28346

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2050

European-Non Finnish (NFE) AF: 0.00000303 AC: 1 AN: 330516

Other (OTH) AF: 0.00 AC: 0 AN: 27766

⚠️ 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 Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	15
DANN	Benign	0.84
PhyloP100		4.3

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: rs141995027; hg19: chr2-179296624;