rs573551830

Variant names:

• chr2-178451719-C-G
• rs573551830
• NM_001042702.5:c.-73C>G

Your query was ambiguous. Multiple possible variants found:

• chr2-178451719-C-G
• chr2-178451719-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001042702.5(PJVK):​c.-73C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000111 in 813,282 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: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: PJVK NM_001042702.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0610
• Publications: 0 publications found

Genes affected

PJVK (HGNC:29502): (pejvakin) The protein encoded by this gene is a member of the gasdermin family, a family which is found only in vertebrates. The encoded protein is required for the proper function of auditory pathway neurons. Defects in this gene are a cause of non-syndromic sensorineural deafness autosomal recessive type 59 (DFNB59). [provided by RefSeq, Dec 2008]

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]

PRKRA Gene-Disease associations (from GenCC):

• dystonia 16

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042702.5. 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
	PJVK	NM_001042702.5	MANE Select	c.-73C>G		5_prime_UTR	Exon 1 of 7	NP_001036167.1	Q0ZLH3
	PJVK	NM_001353775.2		c.-122C>G		5_prime_UTR	Exon 1 of 7	NP_001340704.1
	PJVK	NM_001353777.1		c.-385C>G		5_prime_UTR	Exon 1 of 7	NP_001340706.1	A0PK15

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PJVK	ENST00000644580.2	MANE Select	c.-73C>G		5_prime_UTR	Exon 1 of 7	ENSP00000495855.2	Q0ZLH3
	PJVK	ENST00000970493.1		c.-185C>G		5_prime_UTR	Exon 1 of 8	ENSP00000640552.1
	PJVK	ENST00000642492.1		c.-608C>G		5_prime_UTR	Exon 1 of 8	ENSP00000496267.1	A0PK15

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000111 AC: 9 AN: 813282 Hom.: 0 Cov.: 14 AF XY: 0.0000106 AC XY: 4 AN XY: 376146

African (AFR) AF: 0.00 AC: 0 AN: 15392

American (AMR) AF: 0.00 AC: 0 AN: 958

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5016

East Asian (EAS) AF: 0.00 AC: 0 AN: 3556

South Asian (SAS) AF: 0.00 AC: 0 AN: 16054

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 274

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1580

European-Non Finnish (NFE) AF: 0.0000121 AC: 9 AN: 743798

Other (OTH) AF: 0.00 AC: 0 AN: 26654

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.6
DANN	Benign	0.72
PhyloP100		0.061
PromoterAI		0.033	Neutral

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: rs573551830; hg19: chr2-179316446;